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In this review we discuss the different meanings of the term ‘malaria’ and urge writers and readers to distinguish accurately between them. The distinction is important in clinical practice, clinical trials, epidemiology, and the evaluation of control programs. Both over- and underdiagnosis of malaria as the cause of a disease episode are inevitable; overdiagnosis is common in high-transmission areas and underdiagnosis is common in areas with little or no transmission. Parasite density thresholds, attributable fractions, and clinical algorithms have played important but only partial roles in strengthening diagnosis. Methods by which malaria infection could be confidently identified as the cause, rather than an irrelevant accompaniment, of an illness, are important targets for research. One such ‘signature’ is a distinctive retinopathy that occurs in severe malaria and not in clinically similar diseases. Other indicators of a malarial etiology of clinical disease are needed to strengthen clinical and scientific approaches to the control of malaria.