This chapter addresses perianal painful conditions encountered in the ED setting. Laxatives are the initial therapy for perianal pain from a variety of conditions. Topically applied nitroglycerin is widely recommended for pain caused by either anal fissures or thrombosed external hemorrhoids. The utility of NSAIDs in post-hemorrhoidectomy pain is demonstrated by trials of perioperative administration of agents such as ketorolac and diflunisal. For patients with chronic anal fissure or painful external hemorrhoids who fail nitroglycerin therapy, or who have intolerable side effects to the drug, calcium channel blockers have been recommended as an alternative means to reduce anal tone and relieve symptoms. Perianal pain may also be the presenting complaint for patients with Condylomata acuminatum.The systemic condition lichen sclerosus, usually treated with potent topical corticosteroids, causes perianal (and vulvar) pain that can be significantly alleviated with topical 1% pimecrolimus cream.