The disclosure provides methods for the treatment and prevention of periodontal disease. In preferred embodiments, the invention provides for local treatment of periodontal tissues with a pharmaceutical composition including an immune response modifier (IRM) selected from the group of immune response modifiers comprising imidazoquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, imidazonaphtyridine amines, oxazoloquinoline amines, thiazoloquinoline amines and 1,2-bridged imidazopyridine amines.