Human immunodeficiency virus (HIV)-related cutaneous and anogenital disease in the highly active antiretroviral therapy (HAART) era presents challenging problems for dermatologists. Immune reconstitution-associated diseases (IRADs) are common and important consequences of HAART. Dermatologists should be aware of the cutaneous manifestations of IRAD. The prevalence of clinical human papillomavirus (HPV)-related disease is increased in HIV and does not appear to be diminished by HAART. Many patients on HAART are dogged by persistent cutaneous warts. Anogenital precancer is also common in HIV and may be burgeoning with HAART. Clinicians should be aware of the increased risk of cervical, penile and vulval/vaginal cancers in treated and untreated patients with HIV. The increase in HPV infection in HIV-infected individuals may be, at least partly, due to increased exposure to diverse HPV types, particularly high-risk types that might be able to persist for longer in anogenital regions. Alternatively, persistent/emergent HPV disease in HIV infection might represent persistent or modulated immunodysregulation after HAART and be viewed as a form of IRAD. The immunopathogenesis of HPV IRAD is fascinating and possibly determined by host genotype.