Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) show indisputable promise as chemopreventive agents. Possible targets include cancers of the colon, stomach, breast and lung. However, recent studies raise concern about potential cardiovascular toxicity associated with the use of NSAIDs that specifically target the enzyme cyclooxygenase 2. These findings, and others that show that inherited genetic characteristics might determine preventive success, argue for new strategies that are tailored to individual medical history and genetic make-up.