There are no known pathognomonic nail signs of human immunodeficiency virus (HIV) infection. However, several presentations should increase the index of suspicion. (1) Proximal white subungual onychomycosis or superficial white onychomycosis, especially of the fingernails, is present. Trichophyton rubrum appears to cause both most commonly in HIV-infected patients. Periungual dermatophyte involvement and involvement of all 10 fingernails is unusual in non-HIV-infected persons. (2) Candida is a primary pathogen of the nail bed and nail plate especially if many nails are involved. (3) A destructive, almost granulomatous-like psoriatic involvement of the nails is present. (4) Squamous cell carcinoma of the nail bed in a young adult. There are no clinical trails to confirm the efficacy of therapy mentioned in this article. The treatment suggestions are empirical and are the personal views of the authors.