The free radical scavenging activity of capsaicin (CAP), which is the pungent component of hot chili peppers, has been studied in aqueous and lipid solutions, using the density functional theory. Different mechanisms of reaction have been considered: single electron transfer (SET), hydrogen transfer (HT), and radical adduct formation (RAF). Rate constants and branching ratios of the different channels of reaction are provided, as well as an interpretation of the UV-vis spectra. CAP is predicted to react faster in aqueous solution than in nonpolar media with oxygenated free radicals, and it was found to be a more efficient scavenger than melatonin and caffeine. It was also found that while SET does not contribute to the overall reactivity of CAP toward (•)OOH, (•)OOCH(3), and (•)OCH(3) radicals, it might be important for the reactions with more electrophilic radicals such as (•)OH, (•)OCCl(3), and (•)OOCCl(3). The main process, responsible for the peroxyl scavenging activity of CAP, was found to be the HT from the OH phenolic group. For the reaction with (•)OCH(3), on the other hand, the HT from allylic sites are predicted to be the main channels of reaction. In this particular case a wider product distribution is predicted. This supports the role of the reacting free radical on the preponderant mechanism of action of free radical scavengers.