Molluscum contagiosum is highly prevalent in children and is the most common human disease resulting from poxvirus infection. Swimming pools are a common vector for transmission. Atopy and compromise of skin integrity increase the risk of infection. Genital lesions are more frequent in adults, to whom the virus may be transmitted by sexual contact. The incubation period ranges from2 weeks to 6 months, with an average of 2–7 weeks. In most cases, the disease is self-limited and regresses spontaneously after 3–4 months in immunocompetent hosts. There are no systemic complications, but skin lesions may persist for 3–5 years. Molluscum contagiosum can be associated with immunosuppression and is frequently seen among HIV-infected patients (Chap. 189). The disease can be more generalized, severe, and persistent in AIDS patients than in other groups. Moreover, molluscum contagiosum can be exacerbated in the immune reconstitution inflammatory syndrome (IRIS) associated with the initiation of antiretroviral therapy.