The introduction of new therapies into the clinical arena often requires that prescribing clinicians determine how these new treatments should be integrated into an existing standard of care, typically with little more than clinical trial data to guide them. However, trial outcome measures may not always translate easily into useful information for the practicing physician. Since the publication of dementia treatment guidelines in 2001, new data on Alzheimer's disease (AD) therapies have become available. Notably, memantine has emerged as the first medication indicated for the moderate-to-severe stages of AD. This review summarizes pivotal clinical trial data on memantine in the treatment of moderate-to-severe AD and describes how these results may be interpreted for use in the clinical treatment setting. The studies showed that memantine, both alone and in combination with donepezil, was associated with positive, clinically relevant effects on cognitive and functional ability. Further, memantine in combination with donepezil also was significantly better than donepezil alone in management of behavioral symptoms. This review will conclude with a discussion of how new data on AD treatments will potentially change current treatment parameters.