Abstract: The emergence of electronic health records (EHRs) provides a good opportunity for clinical studies to be carried out on large samples with high efficiency and at low costs. However, misunderstanding and inappropriate application of EHRs in clinical research are common. This paper brings us back to the essentials of epidemiology. We use a number of examples to discuss: the characteristics of EHRs, the relationship of data domains of EHRs with their corresponding variables (exposure, outcomes, and covariates) in epidemiological research, and how to use EHRs to estimate prevalence and incidence and to evaluate the effectiveness of treatment and policy. We also focus on the selection bias and confounding controls, especially unmeasured confounding controls. Hopefully, this paper would contribute to the integration of EHRs and clinical research and to the improvement of efficiency and quality of clinical research.