Combination therapy for HIV-1 infection can reduce viremia to undetectable levels, suggesting that prolonged treatment might eradicate the infection. However, one potential mechanism for viral persistence involves the establishment of a state of latent infection. Recent studies have directly confirmed that HIV-1 establishes a state of latent infection in resting memory CD4+T cellsin vivo. This reservoir is likely to frustrate current efforts to eradicate the infection with combination therapy.