Major depressive disorder (MDD) is a heterogeneous disease which is why there are currently no specific methods to accurately test the severity, endophenotype or therapy response. This lack of progress is partly attributed to the complexity and variability of depression, in association with analytical variability of clinical literature and the wide number of theoretically complex biomarkers. The literature accessible, indicates that markers involved in inflammatory, neurotrophic and metabolic processes and components of neurotransmitters and neuroendocrine systems are rather strong indicators to be considered clinically and can be measured through genetic and epigenetic, transcriptomic and proteomic, metabolomics and neuroimaging assessments. Promising biologic systems/markers found were i.e., growth biomarkers, endocrine markers, oxidant stress markers, proteomic and chronic inflammatory markers, are discussed in this review.Several lines of evidence suggest that a portion of MDD is a dopamine agonist-responsive subtype. This review analyzes concise reports on the pathophysiological biomarkers of MDD and therapeutic reactions via peripheral developmental factors, inflammative cytokines, endocrine factors and metabolic markers. Various literatures also support that endocrine and metabolism changes are associated with MDD. Accumulating evidence suggests that at least a portion of MDD patients show characteristics pathological changes regarding different clinical pathological biomarkers. By this review we sum up all the different biomarkers playing an important role in the detection or treatment of the different patients suffering from MDD. The review also gives an overview of different biomarker’s playing a potential role in modulating effect of MDD.