Background: Neuroimaging studies have revealed structural and functional changes in brain regions associated with major depressive disorder (MDD). These abnormalities appear to be more common and extensive in patients with late-life depression than in younger patients. It has therefore been hypothesized that different morphometric and pathological changes may be associated with MDD, depending on age. Methods: This review stratifies the findings of the various studies on cell morphology in MDD according to age and assesses any possible differences in neuronal and glial cell changes in younger and older age groups. Results: Recent morphological studies in postmortem tissue have revealed alterations in neuron and glial cell populations in the frontal and subcortical circuitry associated with depression. These may differ by age, with glial reduction consistently reported in younger groups in cortical areas and neuronal changes identified in studies with older subjects. Conclusions: Apparent differences in the morphological changes between younger and elderly patients may suggest a differing pathological basis in MDD, dependent on age.