Quality-adjusted life years (QALYs) have been used in the assessment of health interventions for three decades. The popularity of the QALY approach has been constantly increasing, although the debate on its theoretical underpinnings and practical implications is still ongoing. Disability-adjusted life years (DALYs), also widely debated, were shaped some 20 years later, broadly within the same conceptual framework but with a number of important differences. This paper provides a comprehensive formulation of QALY calculation methods, offering practical instruments for assessing the impact of health interventions, similar to those made available elsewhere for calculating DALYs. Systematic differences between QALYs and DALYs are explained by reference to two examples: the prevention of tuberculosis and the treatment of bipolar depression. When a health intervention is aimed at preventing or treating a non-fatal disease, the relationship between QALYs gained and DALYs saved depends on age of onset and duration of the disease, as well as the quality of life and disability weights. In the case of a potentially fatal disease, a larger number of factors may determine differences between outcomes assessed with the two metrics. The relative importance of some of these factors is discussed and illustrated graphically in the paper. Understanding similarities and differences between QALYs and DALYs is important to researchers and policy makers, for a sound interpretation of the evidence on the outcomes of health interventions.