Microorganisms isolated from marine habitats are proving to be an extremely rich source of structurally novel bioactive secondary metabolites. In order to explore and exploit this abundant resource of new natural products, our group has been building a library of culturable microorganisms that we have obtained from both tropical and temperate marine sediment and coral reef environments. Crude organic extracts prepared from laboratory cultures of these microorganisms have been screened in a variety of assays designed to find lead compounds for the development of new drugs for treating human diseases. The lecture will describe the isolation, structure elucidation, synthesis, and biological activities of two new families of secondary metabolites, the plectosphaeroic acids and the turnagainolides, that have been discovered using assays to look for inhibitors of indoleamine 2,3-dioxygenase (IDO) and activators of the inositol phosphatase SHIP. The plectosphaeroic acids are complex alkaloids (plectosphaeroic acid A has a molecular formula of C39H32N6O10S2) and the turnagainolides are cyclic depsipeptides with an unprecedented beta hydroxy carboxylic acid containing residue.