Molluscum contagiosum (MC) is common in human immunodeficiency virus (HIV) seropositive and immunocompromised patients. This study evaluates the current literature concerning the clinical features of MC in this population, the utility of MC as a predictor of immunocompromised state and the natural history of MC and HIV in patients with these co-morbidities. PubMed database search for English-written original studies found 10 of them, all enrolled for HIV patients. There was no unique feature of MC in adult HIV patients; nevertheless, the appearance of MC lesions in adult men should require evaluation for immunocompromised state. In HIV-positive patients, MC tends to occur during the advanced phase of the disease. MC in children is rarely associated with immunodeficiency and usually no further evaluation is needed. In patients with known HIV infection, the presence of MC may signify advancing immunosuppression.