Ulcerative colitis (UC) is a relapsing and remitting chronic inflammatory disease of the large intestine characterized by bloody diarrhea, abdominal pain, urgency, and tenesmus. Rapid induction and maintenance of remission are the primary goals of treatment. Azathioprine (AZA), a purine analog, has been utilized as an immuno-modulator to maintain remission in UC. AZA has been used for a long time, but there is still controversy about its effectiveness, drug interactions, and side effects in people with UC. We conducted a comprehensive analysis of the literature and present a detailed insight into the role of AZA in patients with UC.