Adherence to treatment is currently of main concern for HIV/AIDS control, being associated with treatment success or failure. This systematic review highlights that adherence to treatment is a concept that traditionally refers only to antiretroviral medication intake and attendance at medical appointments. However, these aspects do not reflect the complexity of this topic. There is evidence about the relation between adherence to treatment and other factors that could facilitate or hinder its effectiveness but usually this evidence is not conclusive. In this review, an integral concept of adherence to treatment for HIV/AIDS infection is proposed, considering several simple and complex competences necessary to carry out the therapeutic regime. Additionally, factors with stronger empirical support associated with adherence are identified, including those related to the patient, the health system, the illness and the treatment, as well as social-interpersonal and cultural factors. The aim of this review is to propose new guidelines to evaluate adherence to treatment for HIV/AIDS infection and factors that are associated to it, in order to allow the design of more effective interventions.