Since the era of Gaupp who introduced the concept of atheroscletic depressive disorder, the concept of late-life depression has been correlated with cerebrovascular comorbidities, microvascular lesions, frontal cortical and subcortical gray and white matter hyperintensities. The predominant neuropsychological deficits concern the domains of planning, organization and abstraction, with executive dysfunction being the predominant finding. MRI studies reveal a higher prevalence of white matter lesions in elderly patients with depression. Molecular mechanisms underlying the disease still remain unclear. Hyperhomocysteinemia has been associated with depression through its toxicity to neurons and blood vessels. Endothelial dysfunction is another possible mechanism referring to the loss of vasodilatation capacity. Inflammatory phenomena, such as increased peripheral leucocytes, elevated CRP and cytokine levels, could play a role in endothelial dysfunction. In this review we will briefly combine findings from neurobiological, epidemiological, structural and post-mortem data. A more complex model in late-life depression combining different modalities could be an elucidating approach to the disease's etiopathogeny in the future.