The availability of combination antiretroviral therapy (HAART) has been associated with dramatic decreases in HIV-related morbidity and mortality. These clinical benefits are probably mediated by a decrease in HIV-1 replication and an increase in the number and function of peripheral blood CD4+ lymphocytes. Despite many years of maintaining plasma HIV-1 RNA levels below the limits of detection, many patients do not achieve normal CD4+ lymphocyte counts. A larger proportion of patients who delay HAART for longer have incomplete numerical CD4+ restoration compared to patients who start therapy earlier. Even in patients who normalize their CD4+ lymphocytes insert counts, immune function remains impaired among those who delay HAART for longer periods. Whether subclinical immune deficiency will be associated over longer periods of follow-up with adverse clinical outcomes such as an increased number of infections and malignancies remains to be determined. If prolonged subclinical immunodeficiency is associated with adverse outcomes, the use of immune-based therapies may benefits patients while helping us ascertain the residual deficits responsible for incomplete immune restoration.