Bioactive chemicals are finding increasing use in a research paradigm that emphasizes the value of these as probes. This follows from the tenet that in order to understand a system we must perturb it. Cell-based screens are well suited to finding new bioactive chemicals but the challenge is in understanding mechanism of action. Brown lab researchers are innovators in the development of platforms for hypothesis generation – genetic enhancement and suppression of chemical-induced phenotypes as well chemical-chemical interaction profiling and metabolite suppression – and are accomplished practitioners of chemical biology. No one approach is a panacea and so the Brown group continue to innovate with creative new platforms in the area of chemical genomics.