The pathobiology of psychiatric disorders remains mostly obscure. Diagnosis is often imprecise and current treatments are empirical and at best symptomatic. The identification of biomarkers can help with developing improved drugs and establishing more precise disease diagnoses. Proteins are prime biomarker candidates, because of the central role they play in both, disease etiology and treatment. Today's high throughput methods are capable to detect potential biomarkers by screening complex proteome mixtures of different disease states. A meaningful interpretation of the candidates is indispensable for deeper insights into affective disorders and requires investigation on multiple levels of the cellular system. Thus a systems biology approach is critical to understand and explain the behavior of biomarker candidates and to make use of them in psychiatry.