Adult-generated hippocampal neurons are required for mood control and antidepressant efficacy, raising hopes that someday we can harness the power of new neurons to treat mood disorders such as depression. However, conflicting findings from preclinical research-involving stress, depression, and neurogenesis-highlight the complexity of considering neurogenesis as a road to remission from depression. To reconcile differences in the literature, we introduce the "neurogenic interactome," a platform from which to consider the diverse and dynamic factors regulating neurogenesis. We propose consideration of the varying perspectives-system, region, and local regulation of neurogenesis-offered by the interactome and exchange of ideas between the fields of learning and memory and mood disorder research to clarify the role of neurogenesis in the etiology and treatment of depression.