Combination antiretroviral therapy suppresses HIV-1 replication, but is not curative because of the persistence of both residual viremia and long-lived cells carrying latent, intact proviruses. Recent data, however, have highlighted the substantial impact of early initiation of combination antiretroviral therapy on the number of HIV-1-infected cells that persist after treatment and on the possibility of post-treatment control of viral replication. The well-publicized case of the "Mississippi baby" has fueled great interest in outcomes following immediate initiation of combination antiretroviral therapy in both infants and adults. Here, we review current knowledge of the impact of combination antiretroviral therapy on HIV-1 reservoirs, with specific focus on the timing of treatment initiation. We propose that early initiation of combination antiretroviral therapy is likely to promote the efficacy of strategies to achieve long-term, therapy-free remission of HIV-1 and that this possibility should be considered in decisions about when to initiate the therapy.