Emergency medicine physicians are uniquely positioned to detect manifestations of human immunodeficiency virus (HIV) disease in the head and neck region. Awareness of the myriad of opportunistic infections and malignancies that involve the head, neck, and eyes is paramount to their diagnosis and treatment. On occasion some of these manifestations are a direct result of HIV and represent the initial signs of primary HIV infection. In some cases, prompt diagnosis and therapy will lead to preservation of function and prevention of significant morbidity.