Background: Hippocampal volume reduction has been reported inconsistently in people with major depression. Aims: To evaluate the interrelationships between hippocampal volumes, memory and key clinical, vascular and genetic risk factors. Method: Totals of 66 people with depression and 20 control participants underwent magnetic resonance imaging and clinical assessment. Measures of depression severity psychomotor retardation, verbal and visual memory and vascular and specific genetic risk factors were collected. Results: Reduced hippocampal volumes occurred in older people with depression, those with both early-onset and late-onset disorders and those with the melancholic subtype. Reduced hippocampal volumes were associated with deficits in visual and verbal memory performance. Conclusions: Although reduced hippocampal volumes are most pronounced in late-onset depression, older people with early-onset disorders also display volume changes and memory loss. No clear vascular or genetic risk factors explain these findings. Hippocampal volume changes may explain how depression emerges as a risk factor to dementia.