This thesis describes the development of a rapid antistaphylococcal bioassay and chemical investigation of antistaphylococcal extracts derived from marine invertebrates collected from northern New South Wales. This thesis is divided into three sections. Chapter 2 describes the development of a novel HTS antistaphylococcal bioassay and the subsequent screening of a marine invertebrate extract collection using the developed assay. Chapters 3-7 report on the isolation and structure elucidation of natural products from antistaphylococcal extracts derived from three sponges and two bryozoans. Finally, in chapter 8, the isolated natural products were investigated to determine if they were active against Staphylococcus aureus. The MIC80 of active compounds were reported as was the bacteriostatic or bactericidal mode of action of these bioactive compounds.