The Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) was revised based on a combination of a categorical and a dimensional approach such that in the DSM, Fifth Edition (DSM-5), depressive disorders have been separated as a distinctive disease entity from bipolar disorders, consistent with the deconstruction of Kraepelinian dualism. Additionally, the diagnostic thresholds of depressive disorders may be reduced due to the addition of “hopelessness” to the subjective descriptors of depressed mood and the removal of the “bereavement exclusion.” Manic/hypomanic, psychotic, and anxious symptoms in major depressive disorder (MDD) and other depressive disorders are described using the transdiagnostic specifiers of “with mixed features,” “with psychotic features,” and “with anxious distress,” respectively. Additionally, due to the polythetic and operational characteristics of the DSM-5 diagnostic criteria, the heterogeneity of MDD is inevitable. Thus, 227 different symptom combinations fulfill the DSM-5 diagnostic criteria for MDD. This heterogeneity of MDD is criticized in view of the Wittgensteinian analogy of language game. Depression subtypes determined by disturbances in monoamine levels and the severity of the disease have been identified in the literature. According to a review of the Gottesman and Gould criteria, neuroticism, morning cortisol, cortisol awakening response, asymmetry in frontal cortical activity on electroencephalography (EEG), and probabilistic reward learning, among other variables, are evidenced as endophenotypes for depressive disorders. Network analysis has been proposed as a potential method to compliment the limitations of current diagnostic criteria and to explore the pathways between depressive symptoms, as well as to identify novel and interesting relationships between depressive symptoms. Based on the literature on network analysis in this field, no differences in the centrality index of the DSM and non-DSM symptoms were repeatedly present among patients with MDD. Furthermore, MDD and other depressive syndromes include two of the Research Domain Criteria (RDoC), including the Loss construct within the Negative Valence Systems domains and various Reward constructs within the Positive Valence Systems domain.