Systemic lupus erythematosus is characterized by autoantibodies and immune complex deposition. Several autoantibodies against mainly nuclear autoantigens have been described. One of these nuclear autoantigens is the Smith antigen. In this review, we focus on the position of autoantibodies against the Smith antigen in the classification criteria, the characteristics of the antigen, the production of anti-Smith antibodies in SLE and we discuss the different test methods available, together with their pitfalls, to detect these autoantibodies.