Anal pain is a common complaint for which patients are evaluated in the primary care or emergency room setting. This nonspecific symptom has a broad differential, including anal fissures, internal or external hemorrhoids, perianal abscesses or fistulas, rectal or anal malignancy, labial or vulvar malignancy, anorectal sexually transmitted infections, rectal prolapse, and inflammatory bowel disease. Navigating through this array of diseases quickly and efficiently can pose a challenge for busy primary care and emergency room clinicians. However, with a thorough history, review of systems, and exam, the most likely diagnosis can usually be ascertained. Caution should be exercised when performing digital rectal exam. Surgical referral should be considered when conservative management has failed, the diagnosis is uncertain, or the presentation is atypical.