The field of mood disorders neuroimaging is vibrant, productive and at times chaotic. This chapter first addresses the clear variance between structural and functional neuroimaging study findings of depression and bipolar disorder. When reviewing the mood disorders neuroimaging literature to date, one can appreciate a consistent set of brain regions (including gray and white matter components) as critical to normal and abnormal mood regulation. The consistency across imaging studies in location of abnormality, if not always direction, provides a useful starting point for future investigation. The chapter suggests two primary goals for a mood disorders imaging research agenda: increasing the signal-to-noise ratio for structural and functional imaging studies through technological developments, large-scale multi-center trials and novel analytic methods; and shifting from hypothesis-free to hypothesis-guided investigations based within developing neural network models. It is expected that neuroimaging findings will be able to play a vital role in diagnosis, and treatment development.