AbstractThe Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health shows great promise in providing guidance for research on mental illness but has prompted considerable controversy. Papers by Yancey, Venables, and Patrick and Kozak and Cuthbert illustrate and clarify a number of important features of RDoC. The present commentary evaluates the former paper in light of the latter paper and addresses several common misunderstandings about RDoC. The concept of endophenotypes and diverse psychophysiological approaches will likely be central in RDoC‐inspired research.