Depression is one of the most common psychiatric conditions affecting numerous individuals in the world. However, the currently available antidepressant medication shows low response and remission rates. Thus, new antidepressants need to be discovered or developed. Aiming to describe the current neurobiological hypotheses regarding the pathophysiology of depression and in order to give an overview of novel possible antidepressant drug targets, we reviewed publications and studies referring to the neurobiology of depression. This review included genetics, epigenetics and gene expression, neuroanatomy and structural anatomy, neurochemistry, neuroendocrinology, neuroimmunology and novel drug targets using a MEDLINE/Pubmed search. The search was augmented by a manual search of bibliographies, textbooks, and abstracts from recent scientific meetings. On the one hand, the literature reveals in part contradictory information, but on the other hand, it shows convergent information regarding the relevance of research targets apart from the monoamine deficiency hypothesis of depression such as epigenetic phenomena and changes in neuronal and glial function and structure. Recent neurobiological findings in these areas of research provide multidimensional perspectives for the progress in the psychopharmacological treatment of depression.