Novel Australian biodiversity is being examined as a potential source of new therapeutic agents. Drug discovery begins with attempts to find a molecule that causes a specific biological response, i.e., a “hit.” The trend in drug discovery is clearly towards rapid, high‐throughput screening (HTS) of large libraries of compounds. A particularly attractive option for HTS targets that has become available with the ability to clone human genes is to utilise human targets in the screening process. There is increased probability that the compounds discovered would be more effective in their eventual human target than may be the case for compounds discovered using animal models or, indeed, animal gene products. HTS strategies involve screening of compound libraries, combinatorial libraries, and natural product extracts. The limiting factor in HTS is the ability to access large numbers of chemically diverse substances. Natural products are the greatest source of structural diversity. HTS of the unparalleled diversity in natural product extracts thereby offers one of the best chances for discovery of novel lead compounds and is complementary to the newly emerging source of compounds provided by combinatorial chemistry. However, the complexity of natural product extracts brings with it the added effort required to obtain a single pure compound.