Over the past 10 years, studies of marine-derived bacteria have convincingly shown that these organisms are a prolific resource for structurally-novel secondary metabolites. Unprecedented structures with significant bioactivities are now being defined for applications to numerous diseases including the treatment of cancer and the discovery of new antibiotics effective against drug resistant human pathogens. While many of these compounds are significant and could be solid drug leads, a lack of information defining their mechanisms of action and protein targets reduces interest. As a result, many unique substances are subsequently not developed. In a attempt to improve on this situation, we are now examining the MOAs and protein targets of new bioactive agents earlier in the developmental process. In this presentation, the results of three studies will be illustrated leading to both interesting new targets and old targets of little interest. By taking an early MOA approach, it is hoped that mechanistically-unique drug candidates can be identified at an early stage.