Primary or acute human immunodeficiency virus type 1 (HIV-1) infection is the stage of disease when virus first disseminates throughout the body of newly infected individuals. This process results in the seeding of lymphoid tissue and the central nervous system, and the induction of a specific humoral and cellular immune response. The high level of viremia and associated immune response is often accompanied by an acute illness referred to as the acute retroviral syndrome. This syndrome often includes fever, myalgia, rash, sore throat, and lymphadenopathy. The diagnosis is confirmed by the presence of high levels of HIV in blood along with an undetectable or evolving humoral immune response. Identification of this syndrome allows for the interruption of transmission, early diagnosis and treatment, as well as the opportunity to analyze subjects at a time when the virus and immune system first interact. Studies of the virology and immunology of acute HIV infection, as well as the effect of therapy during this stage of disease has provided new insights into the pathogenesis of HIV infection. Moreover, these studies have advanced our understanding of the successes and failures of the immune response to HIV. Investigations of what constitutes an effective immune response to HIV will be vital to the success of vaccine development in the future.