Acute infection with HIV is symptomatic in approximately two thirds to three-fourths of patients. This stage is defined as primary HIV infection or acute HIV illness. The diagnosis is crucial for public health because counseling can be provided to reduce the risk of transmission and for individual because early antiretroviral treatment could improve the prognosis, slowing the rate of disease progression. Physicians should be aware of the broad clinical spectrum representative of primary HIV infection, which ranges from mild symptoms resembling classic mononucleosis infection to highly severe presentations. Progression to AIDS and to death has been associated with the severity of the acute HIV infection. Clinical trials with combined antiretroviral drugs are needed to identify the best drug combinations as well as the optimal duration of treatment.