The autoimmune connective tissue disease antisynthetase syndrome (ASS) is an inflammatory myopathy associated with myositis-specific autoantibodies, e.g. anti-tRNA-synthetase antibodies (ASA). Since 1976 eight different ASA have been rigorously identified, of which anti-hystidyl-tRNA synthetase (anti-Jo1) is the most prevalent. Other phenotype features of ASS include interstitial lung disease (ILD), Raynaud's phenomenon, polyarthritis, fever, and mechanic's hands. The clinical presentation of ASS varies greatly, as does the severity of involvement of different organs-both among patients and/or over the course of the disease. ILD has been associated with poor outcomes, but in general the heterogeneity of ASS prevents identification of robust prognosis indicators. Early identification of patients requiring aggressive immunosuppressive treatment is very challenging, and there are very few prospective trials available to help match treatment management to ASS clinical characteristics. This review will focus on the biological, clinical, functional, and morphological features of ASS associated with patient outcome. Our objective is to use compiled data on these subjects to discuss the usefulness of patient stratification in developing future prospective therapeutic trials.