Antiretroviral drugs have, as any medical therapy, their natural history. They are born by screening or designing of molecules with activity against HIV, their efficacy and safety is investigated by clinical trials, evaluated by regulatory bodies, used by clinical practice, and finally analyzed by quality of care, economic, social and ethical studies. This flow of information is dynamically accumulated, but it may stop if negative results are obtained. The described knowledge pathway implies that specific methods are needed to answer different questions. At the same time, many decisions have to be taken in order to keep the process flowing, including multiple agents, such as drug industries, government departments, clinicians, health care providers and health policy makers. This paper describes a comprehensive conceptual framework, including the "knowledge" on antiretroviral drugs, the "methodologies" needed to generate them, and the underlying processes of "decision making". It proposes the need for a continuum of assessment of these drugs.