Randomised, controlled trial data show that combination antiretroviral therapy for HIV-1 infection benefits people with CD4-cell counts less than 350 cells/microL. Based on currently known risks and benefits, we believe that if CD4-cell counts and viral load are monitored carefully, and highly active antiretroviral therapy (HAART) is started commonly when the CD4-cell count drops below 350 cells/microL, then clinically relevant immune-system damage and progression to AIDS and death can be greatly delayed or prevented. This approach is dictated by three features of HIV-1 infection that are not typical of infectious diseases: no available regimen can eradicate HIV-1; all currently effective regimens may cause undesirable, sometimes life-threatening, toxic effects; and, unless regimens are strictly adhered to, multidrug resistance can develop, limiting future treatment options. If therapy is started too early, cumulative side-effects of the drugs used and the development of multidrug resistance may outweigh the net benefits of the lengthening of life. If therapy is started too late, increases in disease progression and mortality outweigh the risk of adverse events. A patients' activist (MH) and a clinician (CCJC) discuss data that justify this balanced approach and the feasibility of randomised controlled trials to provide clearer answers about when to start treatment.