This review deals with antibiotic treatment of periodontitis. Antibiotic therapy aims at eradicating or controlling specific pathogens in patients with recently diagnosed active periodontitis or a history of recurrent disease, who fail to stabilize after mechanical/surgical therapy. A variety of microbes may cause periodontitis, and the choice of the antibiotic should be guided by accurate microbiological and sensitivity testings. Review of recent literature shows that appropriate systemic antibiotic therapy may increase the chance of healing in patients with recent or high risk of periodontal breakdown. Topical administration of antibiotic should be reserved to selected cases, such as Actinobacillus actinomycetemcomitans infections, in whom it is to be used in conjunction with mechanical treatment.