OBJECTIVES: A number of recent treatment advances have been labelled cures but a consistent definition of cure does not exist in research or clinical practice. The purpose of this study was to review the term cure and establish an operational definition. METHODS: We conducted a systematic literature review to identify uses of the word cure. All relevant definitions were collected in five disease areas of high disease burden: heart disease, human immunodeficiency virus, diabetes, depression, and cancer (prostate and breast). Walker and Avant’s concept analysis method was applied. Frequently used attributes of cure within each disease area were compared and reduced to the fewest number of defining attributes that would differentiate cure from similar concepts. Subsequent steps included identifying ideal, borderline, and related cases, as well as antecedents and consequences of cure. RESULTS: Three defining attributes were identified: complete and permanent remission, reversing or eliminating the underlying cause of disease, and treatment or other interventions no longer being necessary. These attributes of cure set a high benchmark, making cure difficult to be achieved and measured, especially at the individual level. One potential operational definition may be statistical cure—when a patient’s mortality risk returns to that of the general population. This definition is used in epidemiologic modeling studies given sufficiently long follow-up. However, this does not capture the quality-of-life dimension inherent with disease. The recent concept of the quality-adjusted life-year (QALY) shortfall, i.e. the difference between the quality-adjusted life expectancy of a patient with disease versus that of the general population may provide the best operational definition—alleviation of the QALY shortfall. CONCLUSIONS: The concept of cure was assessed to establish an operational definition as more treatments are expected with “curative” intent. Although difficult to measure, we suggest that the best operational definition for cure is the alleviation of the QALY shortfall.