Chronic anal fissure (CAF) is usually associated with internal anal sphincter spasm, the relief of which is central to provide fissure healing. The treatment for CAF has undergone a transformation in recent years from surgical to medical. Both the approaches share the common goal of reducing the spasm. Though surgical treatment has a high success rate, it can permanently impair fecal continence in a large number of patients. Smooth muscle relaxation seems to be a novel way by which more than 60% of the patients can be cured with the topical use of the agents. This treatment is in addition to the normalization of stools mostly. Smooth muscle relaxation is well tolerated, can be administered on an outpatient basis, does not cause any lesion of the continence organ, and subsequently, does not lead to any permanent latent or apparent fecal incontinence. This review encompasses various agents that are used for smooth muscle relaxation. In addition, it describes various clinical studies reported in the literature with their success rates and side effects.