A rich source for the discovery of novel, pharmacologically active natural products have been the terrestrial plants and microbes, accounting for about 85% of the approved natural products in pharmaceutical use, and about 60% of approved pharmaceuticals and new drug applications submission annually. Discovery in the marine environment has lagged due to the difficulty of exploration in this ecological niche. Such exploration began in the 1950's, after technological advances such as scuba diving which allowed collection of marine organisms, primarily to a depth of about 15 m, which was the limit of that technology. Natural products from filter feeding marine invertebrates and in particular, sponges, have proven to be a rich source of structurally unique pharmacologically active compounds, with over 16,000 molecules isolated thus far and a continuing pace of discovery at hundreds of novel bioactive molecules per year. All classes of pharmaceuticals have been represented in this discovery process, including antiprotozoals, pesticides, TGF-beta inhibitors, cationic channel blockers, anticancer, cytotoxic, antiviral, anti-inflammatory and antibacterial compounds. Important biosynthetic pathways found in sponges which give rise to these compounds include the terpenoid, fatty acid, polyketoid, quinone reductase, alkaloid, isoprenoid, and non-ribosomal protein synthase pathways as summarized in this article.