Primary HIV-infection (PHI) encompasses the first 6 months after HIV infection. Phylogenetic analysis demonstrates that PHI accounts for approximately half of onward transmissions. Between 25 and 90 % of patients with PHI present with an acute retroviral syndrome, but asymptomatic or atypical manifestations of PHI are substantially underestimated and occur in up to one third. Signs and symptoms include fever, fatigue, sore throat, exanthema, lymphadenopathy and diarrhea. The unspecific nature of these signs and symptoms preclude a reliable clinical diagnosis. Therefore, an HIV test should be performed routinely amongst persons at risk. The 4th generation Combo test detects PHI in most cases within two to three weeks after infection and should be used for screening. A routine use of the HIV-specific PCR for screening purposes is discouraged. During the last decade early antiretroviral therapy has been recognized as beneficial for patients with PHI and therefore is recommended.