Headache is a common feature in patients with systemic lupus erythematosus (SLE) and represents a significant source of patient discomfort. The exact prevalence of headache in SLE is unknown. The results of different studies widely vary, most likely due to the use of different classification for headache and the lack of controls in most studies. The relationship between headache and SLE is also unclear since it is difficult to determine which degree and type of headaches can be explained on the basis of chronic illness, or as part of the disease spectrum of SLE. No pathogenic mechanism has so far been described that can fully explain headache induced by SLE. The role of circulating cytokines, vascular injury, neuronal damage or antiphospholipid antibodies (aPL) in the development of headache in SLE patients is also a matter of debate. Other concomitant causes such as infection or hypertension should be excluded before assuming that headache is a feature of SLE activity. Therapeutic approach of headache SLE-related remains empirical and based on clinical experience.