Systemic lupus erythematosus (SLE) and psoriasis (Ps) are two clinically distinct diseases with different pathogenesis. However, recent studies indicate some similarities in both clinical presentation and pathogenetic mechanisms. The coexistence of both entities is very uncommon and has not been fully elucidated. Thus, it remains a diagnostic and therapeutic challenge. In fact, drugs used in SLE can induce psoriatic lesions, whereas phototherapy effective in Ps is an important factor provoking skin lesions in patients with SLE. The aim of this work is to discuss in detail the common pathogenetic elements and the therapeutic options effective in both diseases.