Vascular cognitive impairment is considered the second most common form of mental deterioration in the elderly after degenerative dementias. Therapeutic approaches to vascular dementia mainly rely on the identification and treatment of risk factors. A number of drugs have also been tested with the aim of improving or slowing cognitive decline in patients affected by various forms of cerebrovascular disease. Most of these trials have yielded unsatisfactory results. We hypothesize that some of these failures depend on the inclusion of patients with pathophysiologically heterogeneous types of vascular cognitive decline. In this paper, we review some of the most important trials that tested drugs with a preventive or therapeutic aim in vascular dementia patients. Preliminary results suggest that some beneficial effects can be detected only when the trial population is homogeneous on a clinical and pathogenic basis. In particular, subcortical vascular dementia, a form with a rather univocal clinical, radiological, and pathological picture, seems a particularly apt choice as a target for future clinical studies. At present, only one therapeutic trial is being conducted in patients affected by this specific form of vascular dementia.