The first documented case of drug-induced gingival enlargement was reported in 1939. Since that time, specific medications have been associated with this condition. Although the biologic mechanisms responsible for drug-mediated gingival enlargement remain unclear, a multifactorial etiology is considered to be responsible, with contributing factors including age, genetic predisposition, and local conditions. While the role of plaque remains to be completely elucidated, there is abundant clinical evidence demonstrating at least partial resolution of drug-induced gingival enlargement following improved plaque control. Variations in drug kinetics, gingival crevicular fluid concentrations, protein synthesis, and the presence of growth factors also might contribute to the mechanism of gingival overgrowth.