The purpose of this paper is to assess the clinical relevance of the significant results reported in clinical trials of memantine therapy for Alzheimer disease (AD) and vascular dementia. We sought to understand what clinically detectable changes would be evident to the patient with dementia, their caregivers, and the treating physician during a trial of memantine therapy. A literature search was performed on MedLine, PsycInfo, and the Cochrane database. The statistically significant findings from the memantine literature were reviewed using treatment effect size as a measure of clinical meaningfulness. There have been 3 phase 2 studies of memantine in dementia, and 6 phase 3 studies published as of August 1, 2005. Of the 6 published phase 3 trials of memantine in dementia; 2 were in mild-moderate vascular dementia, 1 in mild-moderate AD, 2 in moderate-severe AD, and 1 in severe dementia (both AD and vascular dementia). The most convincing evidence of a clinically meaningful treatment effect of memantine therapy is in the moderate-severe AD patient population. Cognition, as measured by the Severe Impairment Battery, had an effect size of 0.32 and 0.49 in the 2 published trials, indicating a small-to-medium effect of the medication. Global, functional, and behavioral scales also showed a small-to-medium response to memantine.