One of the most controversial topics in the medical management of HIV disease is the optimal time to initiate highly active antiretroviral therapy (HAART) in HIV-1-infected adults. Premature exposure to antiretrovirals may precipitate early evolution of resistance and unnecessary side-effects, whereas remaining off HAART until late in the course of HIV disease may lead to reduced therapeutic benefits and elevated mortality. The lack of a randomised clinical trial to consider this issue has resulted in ongoing revision of expert recommendations and substantial variability between international consensus guidelines regarding the optimal time to initiate therapy. Since this uncertainty is a source of unease for both patients and clinicians, we summarise the latest evidence regarding the optimal time to initiate HAART with consideration of the potential benefits and drawbacks of starting HIV treatment at the different levels presently recommended in leading consensus guidelines.