Central and peripheral biomarkers can be used to diagnose, treat, and potentially prevent major psychiatric disorders. But there is uncertainty about the role of these biological signatures in neural pathophysiology, and their clinical significance has yet to be firmly established. Psychomotor, cognitive, affective, and volitional impairment in these disorders results from the interaction between neural, immune, endocrine, and enteric systems, which in turn are influenced by a person’s interaction with the environment. Biomarkers may be a critical component of this process. The identification and interpretation of biomarkers also raise ethical and social questions. This article analyzes and discusses these aspects of biomarkers and how advances in biomarker research could contribute to personalized psychiatry that could prevent or mitigate the effects of these disorders.