Certain anticonvulsants, cyclosporine, and a variety of calcium channel blockers have been shown to produce clinically and histologically similar gingival enlargements in certain susceptible patients. These drugs appear to be similar with respect to their pharmacologic mechanism of action at the cellular level. The primary target tissue is the most essential difference among them. Therefore it is tempting to speculate that these agents may act similarly on a common secondary target tissue, such as gingival connective tissue, and cause a hyperplastic response. This tissue reaction may involve a disturbance of calcium ion influx into specific cell populations with a resulting alteration in collagen metabolism and other host cell response mechanisms. A connection between ion exchange, folate uptake, collagenase activation, and bacterial inflammation may exist. Until a more effective approach can be developed from future research results, treatment should continue to emphasize plaque control, professional debridement, and resective gingival procedures to improve function, esthetics, and access for home care.