▪ Abstract This review focuses on the current status of biomarkers and/or approaches critical to assessing novel neuroscience targets with an emphasis on new paradigms and challenges in this field of research. The importance of biomarker data integration for psychotropic drug development is illustrated with examples for clinically used medications and investigational drugs. The question remains how to verify access to the brain. Early imaging studies including micro-PET can help to overcome this. However, in case of delayed tracer development or because of no feasible application of brain imaging effects of the molecule, using CSF as a matrix could fill this gap. Proteomic research using CSF will hopefully have a major impact on the development of treatments for psychiatric disorders.