Many anticancer agents kill tumor cells by inducing apoptosis, and improvements in therapeutic strategies will depend on a clear understanding of the molecular mechanisms by which this occurs. To study the role of the Bax protein in drug-induced apoptosis, Zhang et al. used sophisticated genetic approaches to create derivatives of human colorectal cancer cells that were devoid of functional Bax genes. Cells without Bax retained a partial apoptotic response to the chemotherapeutic agent 5-fluorouracil but were completely resistant to apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs), agents currently being used clinically for cancer chemoprevention. This striking requirement for Bax in the cellular response to NSAIDs may have important implications for future cancer chemoprevention strategies, because it suggests that cells can easily develop resistance to this class of drugs.