The critical appraisal of research is a fundamental process for systematically assessing the quality and validity of scientific literature, ensuring evidence-based decision-making in research, clinical practice and public health policy. This chapter guides readers through how to evaluate a molecular epidemiology paper in a structured approach by methodically examining all important aspects of the conducted research. These include the central research question, the study design and population, how results were derived and interpreted, ethical issues, generalisability and potential public health implications. To illustrate each of these points, we undertake a worked example of a critical appraisal for a published paper using molecular and epidemiological data to investigate hospital-acquired SARS-CoV-2 infection in the UK during the first phase of the COVID-19 pandemic is discussed.