The purpose of this study is to review and summarize published information on the use, effectiveness, and adverse effects of cyclophosphamide (CYC) in the management of idiopathic inflammatory myopathies (IIM) and IIM-related interstitial lung disease (IIM-ILD). We performed a systematic search on various databases from May 1975 to May 2014 to find articles concerning CYC therapy in IIM and IIM-ILD. The initial search involved 310 articles, and the 12 articles that met the study criteria were analyzed in detail. All studies were non-randomized. Intravenous CYC (IVCYC) was administered as treatment for IIM in 11 of the studies. Additionally, eight of the twelve studies assessed the effect of CYC in developing resistance steroids or in refractory IIM. IVCYC pulses of 0.3-1.0 g/m(2) or 10-30 mg/kg were applied at weekly to monthly intervals for 6-12 months together with either glucocorticoids or another immunosuppressive agent. According to a comprehensive analysis of the studies, 80.8 % (42/52) and 73.1 % (38/52) of patients showed improvement in muscle strength and function. The CK levels of 87.5 % (35/40) of patients fell. The forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) improved in 57.6 % (34/59) and 64.3 % (27/42) of patients. The high-resolution computed tomography (HRCT) findings improved in 67.3 % (35/52) of patients. IVCYC treatment allowed 58.1 % (25/43) of acute/subacute IIM-ILD patients to survive. However, 18 patients died, and the histopathological findings revealed that the 12 deaths were due to diffuse alveolar damage (DAD). HRCT revealed a ground glass (GrG) pattern in 66.7 % (12/18) of the deaths. Of the patients who died, 70 % (7/10) had pneumomediastinum. IVCYC seems to improve both muscle strength and function and lung function in refractory IIM and IIM-ILD patients, and it appears to be relatively well tolerated and safe.