Depression is one of the most common mental-health disorders, caused by a variety of genetic, biological, environmental, and psychological factors combined. Major depressive disorder (MDD) is typically treated with first-line antidepressant agents that primarily target monoamine neurotransmission; however, only approximately one third of patients with MDD achieve remission following a trial with such an antidepressant. Furthermore, MDD is a heterogeneous phenotype, and new frameworks such as the NIMH Research Domain Criteria (RDoC) may provide a more accurate, biologically based comprehension of the symptomatic heterogeneity of this devastating illness, and certain symptomatic clusters may be promising targets for novel therapeutics, such as drug and psychological treatments for the management of the cognitive impairments that can encompass several domains and contribute to psychosocial function, and that can persist for many patients even in periods of symptomatic remission. Neurobiology of Depression synthesizes the basic neurobiology of major depressive disorder with discussion of the most recent advances in research, including the interacting pathways implicated in the pathophysiology of MDD, omics technologies, genetic approaches, and the development of novel optogenetic approaches that are changing researchers' perspectives and may revolutionize research into depression. The basic foundational understanding of the neurobiology underlying the disorder, as well as the comprehensive summary of the most recent advances in research, combine to aid advanced students and researchers in their understanding of MDD and change the landscape of the management of depression with the development of novel and fast-acting pharmaceutical and neuromodulatory approaches. Aids readers in understanding major depressive disorder in the context of NIMH Research Domain Criteria (RDoC) recommendations Covers range of existing and potential pharmacologic and non-pharmacologic treatment options, from lifestyle adjustments to antidepressants to novel therapeutics Synthesizes discussion of cellular and molecular mechanisms underlying symptoms with clinical aspects of depression for a thorough understanding of the disorder