Mar.Drugs 2014.12 1068 source of structurally diverse bioactive metabolites and have vielded some of the most important active ingredients known today[11].Recently it was even realized that many compounds previously isolated from marine macroorganisms,such as sponges and tunicates,are in fact,metabolic products of associated microorganisms [12.13]. Due to their broad panel of bioactivities such as anti-tumor,anti-microtubule,anti-proliferative. photoprotective,antibiotic and anti-infective [14-19].marine natural products(MNP)are exceptionally interesting high-value ingredients for applications in the pharmaceutical industry and more and more companies are investing in this field.Following the same trend,cosmetics industry is progressively turning to the sea in the search for new ingredients.Traditionally,in the field of cosmetic industry cosmetics were defined as articles to be applied to human body for cleansing,beautifying,promoting attractiveness.or altering the appearance without affecting body structure or functions [201.However. more recently,the cosmetic industry introduced a special class of products.the cosmeceuticals,as a combination of cosmetics and pharmaceuticals,as bioactive ingredients are now combined with creams,lotions and ointments [21].Interestingly,an increasing number of suppliers of the cosmetic industry are being pushed to include extracts made from costal plants,seaweeds,algae and sea minerals into cosmeceutical ingredients.These extracts contain vitamins and minerals and they show ultraviolet and anti-oxidant protection and general anti-aging benefits [22-25].In fact,activities such as antioxidant,anti-wrinkle,anti-tyrosinase and anti-acne are among the most usual activities of marine cosmetic ingredients for skin health [21,26].Hence,an entire new paradigm of beauty care, combining cosmetics and pharmaceuticals properties into novel products with biologically active ingredients,will be the hallmark of the next decades The aim of this review is to outline the role of MNP in pharmaceutical and cosmeceutical industries,to identify the main bottlenecks found during the process of discovery and development. and to give an overview over the compounds that entered successfully in those markets.Tips for success will also be given so that more mne can reach the market 2.Marine Environment as an Unexploited Source for Bioactives Discovery The discovery and identification of the two nucleosides spongothymidine and spongouridine in the early 1950s from the Caribbean marine sponge Cryptotethia crypta paved the way of MNP as promising new chemical entities of potential therapeutic value [27].Since then,several other therapeutic agents have been obtained through isolation from natural sources.by chemical synthesis or a combination of both. In the most traditional process for bioactive discovery,a natural product is firstly extracted from the source,screened against a specific target,isolated by a bioassay-guided isolation procedure. fractionated and purified,yielding essentially a single biological active compound.Despite its widespread use,this traditional method of natural product bioactive discovery is slow,labor intensive barely efficient and provides no guarantee of success.Nowadays,NP discovery is on high demand for rapid screening.hit identification and hit-to-lead faster development processes.being mandatory to explore new approaches in order to compete successfully with other alternative drug discovery methods.In fact,rational drug design involving high throughput screening (HTS)technology in combination with combinatorial chemistry (CC)have reduced in the past decades the interest on NP Mar. Drugs 2014, 12 1068 source of structurally diverse bioactive metabolites and have yielded some of the most important active ingredients known today [11]. Recently it was even realized that many compounds previously isolated from marine macroorganisms, such as sponges and tunicates, are in fact, metabolic products of associated microorganisms [12,13]. Due to their broad panel of bioactivities such as anti-tumor, anti-microtubule, anti-proliferative, photoprotective, antibiotic and anti-infective [14–19], marine natural products (MNP) are exceptionally interesting high-value ingredients for applications in the pharmaceutical industry and more and more companies are investing in this field. Following the same trend, cosmetics industry is progressively turning to the sea in the search for new ingredients. Traditionally, in the field of cosmetic industry cosmetics were defined as articles to be applied to human body for cleansing, beautifying, promoting attractiveness, or altering the appearance without affecting body structure or functions [20]. However, more recently, the cosmetic industry introduced a special class of products, the cosmeceuticals, as a combination of cosmetics and pharmaceuticals, as bioactive ingredients are now combined with creams, lotions and ointments [21]. Interestingly, an increasing number of suppliers of the cosmetic industry are being pushed to include extracts made from costal plants, seaweeds, algae and sea minerals into cosmeceutical ingredients. These extracts contain vitamins and minerals and they show ultraviolet and anti-oxidant protection and general anti-aging benefits [22–25]. In fact, activities such as antioxidant, anti-wrinkle, anti-tyrosinase and anti-acne are among the most usual activities of marine cosmetic ingredients for skin health [21,26]. Hence, an entire new paradigm of beauty care, combining cosmetics and pharmaceuticals properties into novel products with biologically active ingredients, will be the hallmark of the next decades. The aim of this review is to outline the role of MNP in pharmaceutical and cosmeceutical industries, to identify the main bottlenecks found during the process of discovery and development, and to give an overview over the compounds that entered successfully in those markets. Tips for success will also be given so that more MNP can reach the market. 2. Marine Environment as an Unexploited Source for Bioactives Discovery The discovery and identification of the two nucleosides spongothymidine and spongouridine in the early 1950s from the Caribbean marine sponge Cryptotethia crypta paved the way of MNP as promising new chemical entities of potential therapeutic value [27]. Since then, several other therapeutic agents have been obtained through isolation from natural sources, by chemical synthesis or a combination of both. In the most traditional process for bioactive discovery, a natural product is firstly extracted from the source, screened against a specific target, isolated by a bioassay-guided isolation procedure, fractionated and purified, yielding essentially a single biological active compound. Despite its widespread use, this traditional method of natural product bioactive discovery is slow, labor intensive, barely efficient and provides no guarantee of success. Nowadays, NP discovery is on high demand for rapid screening, hit identification and hit-to-lead faster development processes, being mandatory to explore new approaches in order to compete successfully with other alternative drug discovery methods. In fact, rational drug design involving high throughput screening (HTS) technology in combination with combinatorial chemistry (CC) have reduced in the past decades the interest on NP