The initial idea that potent antiretroviral therapies could eradicate HIV infection within a few years of treatment has been recently challenged by the demonstration that the viral reservoir persists in the peripheral blood and in the lymphoid tissue. For this reason, an alternative approach based on the use of interleukin-2 has been developed. This cytokine, in fact, may be able to activate infected cells, promoting viral integration and replication, making HIV susceptible to antiretroviral treatments; this fact may ultimately contribute to the eradication of the virus itself. The measurement of the viral reservoir appears therefore essential to monitor the effects of combination therapies. We summarize here the technical approaches that have been used to quantitatively assess the HIV reservoir. We also show that the prolonged use of IL-2 in association with antiretroviral drugs promotes a reduction of the viral reservoir, but is unable to eradicate HIV, even after two years of therapy. The available in vitro and in vivo data do not exclude the fact that IL-2 may have a future in the treatment of HIV infection, though new therapeutic approaches using different strategies are required to clarify this issue.