The concept of a cryptoglandular origin for most cases of perianal sepsis understates the complexity of the disease and hides various aspects that are important for treatment. At the center of an understanding of the pathophysiology of anal fistulas is knowledge of the anatomy of the anal glands. These are merocrine glands, secreting mucus by exocytosis. There is an average of 4–5 glands per anus, with a range of 2–11. The glands drain into the anal crypt at the dentate line but originate in various locations in the perianal tissues. Most glands are submucosal, passing cephalad from their origin to the crypt. Others begin in the internal sphincter, and a few start in the intersphincteric plane. The percentage of glands that pass completely through the internal sphincter seems to vary from one study to another, perhaps due to the ethnicity of the patients.