Photosensitivity reactions are recognized as unwanted adverse effects of an array of commonly administered topical or systemic medications, including nonsteroidal anti-inflammatory agents, antifungals, and antimicrobials. When a drug induces photosensitivity, exogenous molecules in the skin absorb normally harmless doses of visible and UV light, leading to an acute inflammatory response. In phototoxic reactions, the damage to tissues is direct; in photoallergic reactions, it is immunologically mediated. In vitro and in vivo assay systems can assist in predicting or confirming drug photosensitivity. The incidence of photosensitivity reactions may be too low to be detected in clinical studies and may become recognized only in the postmarketing stage of drug development. Some drugs have been withdrawn because of photosensitivity effects that appeared after general release. Photosensitivity reactions have been studied for a number of topical antimicrobials and for the sulfonamides, griseofulvin, the tetracyclines, and the quinolones. Incidence and intensity of drug phototoxicity can vary widely among the different compounds of a given class of antimicrobials. When phototoxic effects are relatively low in incidence, mild, reversible, and clinically manageable, the benefits of an antimicrobial drug may well outweigh the potential for adverse photosensitivity effects.