The purpose of this review is to provide an update on the most recent research regarding potential causes and treatments for perimenopausal depression. Erratic estrogen fluctuations and alterations in the neurosteroid allopregnanolone are important contributors to perimenopausal mood symptoms. These hormone changes augment increased risk associated with recent stressful events, as well as early life childhood events. Perimenopausal depressions have different clinical presentations and may respond to differential treatment approaches. Future research should focus on these recent findings of interindividual hormonal sensitivity, childhood trauma histories, and varying depression symptom profiles for a personalized treatment approach to perimenopausal depression.