Connective tissue diseases (CTDs) are a group of autoimmune inflammatory disorders, that target different body systems to various extents. The respiratory system is one of the most common systems implicated in various CTDs. The entire respiratory tract, including the lungs, pleura, airways, pulmonary vessels, and respiratory muscles, can be involved [1]. CTDs have a myriad of clinical and radiological manifestations, from acutely inflammatory to progressively chronic and fibrotic [2]. Compared to interstitial lung diseases (ILD) without an underlying CTD, connective tissue disease-associated interstitial lung disease (CTD-ILD) share similar clinical, pathological, and radiological forms, yet differ tremendously in terms of treatment and prognosis. Several pharmacological agents, most commonly azathioprine (AZA), cyclophosphamide (CYC), and mycophenolate mofetil (MMF), have been used to treat these conditions. The latter has been increasingly recognized as the standard immunomodulator for CTD-ILD treatment. The objective of this study is to scrutinize the evidence for AZA use in this population in terms of effectiveness and safety. AZA is a purine analog that is commonly used in combination with corticosteroids to manage various forms of CTD-ILD. However, little data is available to support its use. Similar to other agents, its use is mainly derived from studies conducted on patients with ILDs without an underlying CTD