Major Depressive Disorder (MDD) and antidepressant therapy response are largely based on behavioral criteria, which are known to correlate at best modestly with biological measures. Therefore, it is not surprising that the search for peripheral biological markers (biomarkers) being assessed in distant biological systems such as body fluids has not yet resulted in clinically convincing measures for MDD diagnostics or treatment evaluation. Imaging genetics studies, however, have been successful in the search for intermediate imaging phenotypes of MDD and treatment response that are directly related to the neurobiological underpinnings of MDD, but are not suitable for a broad clinical use today. Hence, we argue that intermediate phenotypes derived from imaging genetics studies should be utilized as substitutes of behaviorally assessed psychiatric diagnoses or therapy response in the search for easily accessible peripheral biomarkers. This article will further cover the current state of peripheral and neural biomarker research.