Systemic lupus erythematosus (SLE) is characterized by a panoply of autoantibodies (more than 50). Some of them are more prevalent (anti-ds DNA > 80%) while others are less frequently detected, but highly specific for SLE (anti-Sm, 20%). In this review we will discuss the clinical significance of anti-RNP, anti-Ro, anti-La and anti-phospholipid antibodies. We will also summarize the clinical and experimental evidence for the pathogenic role attributed to each one of these antibodies.