The inflammatory response represents a first line of defense against invading pathogens and is important to human health. Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease. The chemistry of the inflammatory response is complex and involves the generation of highly reactive oxidants and electrophiles designed to kill the pathogen as well as the release of small molecule and protein mediators of intercellular signaling, chemotaxis, vasoconstriction, and wound-healing. Oxidation of unsaturated fatty acids--either nonenzymatic or enzymatic--contributes to the inflammatory response and associated cellular pathologies. The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer. In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.