Anti-synthetase syndrome (AS) is a rare autoimmune disorder characterized by the presence of aminoacyl-transfer RNA synthetase antibodies in conjunction with clinical features such as interstitial lung disease (ILD), Raynaud's phenomenon, nonerosive arthritis, and myopathy. AS distinguishes itself from other inflammatory myopathies by its significant lung involvement and rapidly progressive interstitial lung disease (AS-ILD), therefore the management of AS-ILD requires careful clinical, serologic and radiologic assessment. Glucocorticoids are considered the mainstay of therapy; however, additional immunosuppressive agents are often required to achieve disease control. Patient prognosis is highly dependent on early diagnosis and symptom recognition as the antibody profile is thought to influence therapy response. Since progressive ILD is the leading cause of morbidity and mortality, this review will discuss the clinical approach to patient with suspected AS, with particular emphasis on diagnosis and management of AS-ILD.