Background Caspases are key mediators of apoptosis. Caspase-8 mediates extrinsic, and caspase-9 initiates the intrinsic pathway of apoptosis. Apoptosis Inducing Factor (AIF), a mitochondrial proapoptotic protein, mediates cell death by a caspase-independent process. Because apoptosis is involved in periodontal disease, this study evaluated caspase-8, -9, and AIF in periodontal disease. Methods Twenty periodontally healthy volunteers (Group Healthy), 20 patients with generalized aggressive periodontitis (Group AgP), and 20 patients with generalized chronic periodontitis (Group CP) were included in this study. Levels of caspase-8, -9, and AIF were evaluated in gingival crevicular fluid (GCF) of all participants via enzyme-linked immunosorbent assays. Results AIF was significantly higher in the AgP (P = 0.07) and CP groups (P = 0.01) than the Healthy group, and similar to the CP and AgP groups (P > 0.05). Caspase-8 was significantly higher in the CP and Healthy groups than the AgP group (P = 0.00), and similar between Healthy and CP groups (P > 0.05). Caspase-9 was significantly higher in the AgP group than the Healthy group (P = 0.01), and similar between Healthy and CP groups (P > 0.05). Conclusions The mitochondrial-centered intrinsic pathway involving caspase-9 and AIF, and the extrinsic pathway involving caspase-8 are significant for aggressive periodontitis. The intrinsic pathway involving caspase-independent AIF is also significant for chronic periodontitis.