Antisynthetase syndrome is characterized by fever, interstitial lung disease (ILD), arthritis that mimics rheumatoid arthritis, a cracking and scaling of the lateral and palmar aspects of the fingers (referred to as mechanic’s hands), and moderately severe myositis. Although polymyositis (PM) and dermatomyositis (DM) have been suspected to be associated with extraskeletal manifestations since the 1950s, it was not until the 1990s that the antisynthetase syndrome was recognized as a separate clinical entity. In 1990, Marguerie et al described for the first time a series of 29 patients with PM/DM who had the characteristic clinical features of ILD, inflammatory arthritis, and Raynaud phenomenon, as well as the presence of antisynthetase antibodies. These antibodies are the most widely recognized myositis-specific autoantibodies. They are directed at aminoacyl-tRNA synthetases, cytoplasmic enzymes that catalyze the binding of amino acids to their cognate tRNAs for incorporation into growing polypeptide chains. To date, eight different anti-antisynthetase antibodies have been described, namely anti-PL-7, anti-PL-12, anti-OJ, anti-EJ, anti-KS, anti-ZO, anti-tyrosyl, and anti-Jo-1. An increased frequency of ILD (50% to 100% vs 10%) and arthritis (60% to 100% vs 30%) has been reported in patients with PM/DM carrying the antisynthetase antibody, compared with patients without the antibody.