Systemic lupus erythematosus (SLE) is usually described as a disease that most often strikes reproductive-age women. However, the onset of SLE beyond the age of 50 years is reported to occur in 3-18% of patients. This later age at onset has a strong modifying effect on the clinical presentation, disease course, response to treatment and prognosis of SLE. In comparison with younger patients, patients with late-onset SLE often have delayed diagnosis and less common occurrence of severe manifestations. For instance, literature data suggest that pulmonary involvement and serositis are more frequent in late-onset SLE, whereas malar rash, photosensitivity, arthritis and nephropathy occur less commonly. Furthermore, some distinct aspects of late-onset SLE may be influenced by the association with Sjögren's syndrome, which is more frequent in the elderly. Not only clinical features but also serological manifestations of SLE change with aging. In comparison with early-onset SLE patients, older patients have a higher frequency of rheumatoid factor and of antinuclear antibody positivity, and a lower frequency of anti-ribonucleoprotein (anti-RNP) and anti-Sm antibody positivity. The major challenge for physicians managing patients with SLE is to treat the active phase without allowing the treatment itself to cause long-term damage. This is especially true in older and often polymedicated patients, in whom side effects of treatments are more frequent. Another important issue is that possible drug interactions should always be considered in the elderly. The management of the disease in these older patients depends on the type and severity of disease manifestations. The use of antimalarial agents such as hydroxychloroquine is an important aspect of SLE treatment, unless contraindicated. Other treatments mostly include NSAIDs, corticosteroids and immunosuppressive agents, depending on which organs are involved. Survival data may be used as an indirect way to assess the changes in the severity of SLE with aging, but the few studies available conclude that late-onset SLE is associated with poorer survival than early-onset SLE, which likely reflects the consequences of aging rather than true differences in survival. Importantly, the cause of death in late-onset SLE patients is usually not SLE itself, but rather the more frequent occurrence of infections, cardiovascular disorders, malignancies or drug-induced complications.