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Cross-sectional studies represent the second line of evidence (after case reports) in the ladder of evidence aimed at defining disease aetiology. This study design is used to generate hypotheses about the determinants of a given disease but also to investigate the accuracy of diagnostic tests and to assess the burden of a given disease in a population. The intrinsic limitation of cross-sectional studies, when applied to generate aetiological hypotheses, is that both the exposure under investigation and the disease of interest are measured at the same point in time. For this reason, generally the cross-sectional design does not provide definitive proofs about cause-and-effect relationships. An advantage of cross-sectional studies in aetiological and diagnostic research is that they allow researchers to consider many different putative risk factors/diagnostic markers at the same time. For example, in a hypothetical study aimed at generating hypotheses about the risk factors for left ventricular hypertrophy (LVH) in patients with chronic kidney disease, investigators could look at several risk factors as potential determinants of LVH (age, gender, cholesterol, blood pressure, inflammation, etc.) with minimal or no additional costs. In this article, we make examples derived from the nephrology literature to show the usefulness of cross-sectional studies in clinical and epidemiological research.