Just before the official launch of the DSM-5 in 2013, the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health was made public and is becoming increasingly more important in psychiatric research. The aim of this paper is to clarify the conceptual approach of RDoC, to systematically discuss limitations, to present exemplary RDoC-based studies and to consider the relevance of the RDoC concepts for clinicians and scientists. The is a qualitative introduction and review article with a critical discussion. The RDoC initiative was not conceived as an alternative diagnostic manual to DSM-5 or IDC-10/11 for use in clinical practice. It is a new systematic framework for psychiatric research based on the most recent results of cognitive neuroscience and aims to map mental disorders dimensionally and transdiagnostically. Despite some weaknesses, it is currently the most elaborated and scientifically grounded approach for multidisciplinary research on mental disorders. In contrast to the purely symptom-based DSM and ICD approaches, which are agnostic with respect to the pathogenesis of mental diseases, the explicit aim of the RDoC initiative is to systematize biological knowledge about risk factors and causes of mental disorders; therefore, it has a much greater potential to develop new and individualized therapeutic strategies based on disease mechanisms.