Periodontitis is a common condition in dogs. Treatment of periodontitis consists of mechanical removal of plaque and calculus by scaling, root planing, and polishing the teeth. Antimicrobial therapy can provide additional improvement in severe or refractory cases of periodontitis when combined with dental prophylaxis if ongoing plaque control is not provided. The ability of various antimicrobials to reach therapeutic levels in the periodontal tissues differs greatly. The efficacy of antimicrobials against common periodontal pathogens also varies greatly. Choosing an appropriate antibiotic to treat periodontitis should be based on these considerations. Amoxicillin-clavulanate, clindamycin, and nitroimidazoles, such as metronidazole and tinidazole, seem to be particularly effective based on pharmacokinetic and clinical studies.