Due to the unparalleled progress in the fields of the pathophysiology and treatment of HIV infection, prognosis for HIV-infected individuals has steadily improved over the last 5-10 years. This could only come about thanks to the many clinical trials which results provided the basis for international HIV and AIDS treatment guidelines pertaining to, among others, the best time to start antiretroviral treatment and the best regimens. These decisions are of utmost importance because when therapy is started and what regimen is applied have great influence on the efficacy of treatment and when it will be necessary to change the regimen, often deciding the fate of the patient. The first antiretroviral regimen is the most efficacious one and is supposed to last the longest. These difficulties are further complicated by potential HIV drug resistance and the side effects of the therapy. Equally important is patient adherence to his doctor's orders, which entail the dosing schedule. Adherence is directly influenced by both the complexity of the drug regimen and the side effects. The guidelines are intended to bring order, at least partially, to the complex decision-making process at the beginning of antiretroviral therapy. Individuals on treatment are often patients being treated in other medical institutions, where they should also receive the necessary motivation to continue therapy and abide by the doctor's orders. Thus it is extremely important to recall the principles of antiretroviral therapy and the problems these patients can encounter. Recent changes in the guidelines are another reason to bring them to mind.