Late life depression (LLD) is an important area of research given the growing elderly population. The purpose of this review is to examine the available evidence for the biological basis of LLD. Structural neuroimaging shows specific gray matter structural changes in LLD as well as ischemic lesion burden via white matter hyperintensities. Similarly, specific neuropsychological deficits have been found in LLD. An inflammatory response is another possible underlying contributor to the pathophysiology of LLD. We review the available literature examining these multiple facets of LLD and how each may affect clinical outcome in the depressed elderly.