A review. An approach to anti-infective drug development taken by PolyMedix replicates the activity of large protein mols. through novel, small-mol. chem., and this imitates innate human immunity. The PolyMedix lead compounds, defensin mimetics, duplicate the activity of host defense proteins but in mols. that are a fraction of the size and complexity of defensins. These defensin mimetics directly cause bacterial cell membranes to rupture, a mechanism that is unique among known antimicrobial compounds A Phase I clin. trial with PMX-30063, the first defensin mimetic being developed, was successfully completed in Dec. 2008. The results of this trial showed that it was possible to safely administer PMX-30063 at doses that resulted in blood levels associated with full efficacy in animal models of infection, without any serious side effects. The other compound currently in clin. development is PMX-60056 'heptagonist,' a reversing agent for heparin and low-mol.-weight heparins. By capturing the salient properties of host defense peptides in a synthetic small-mol. or polymer format, PolyMedix has shown that nature, with a bit of help from computational technol. and human ingenuity, is still a rich source of ideas for new therapies.