Alzheimer's disease is a progressive, degenerative brain disease. As the disease progresses, patients and caregivers face increasing problems with medication adherence. Given its relentlessly progressive nature, newer and more effective therapies for Alzheimer's disease are needed. Memantine 10 mg twice daily is the FDA-approved regimen for the treatment of moderate to severe Alzheimer's disease. The goal of this article is to review the once-daily memantine ER 28 mg formulation for the treatment of Alzheimer's disease, which, by simplifying the dosage regimen, decreases the problems of medication adherence. A new extended-release formulation has been developed to improve adherence and possibly efficacy without compromising an excellent tolerability and safety profile. There is also a possibility of dose-dependent improvement/superiority in cognitive, global and behavioral measures as well as in verbal fluency with higher-dose (28 mg/day) memantine. Readers will become knowledgeable about this new dose and preparation of memantine. However, these advantages remain provisional and more research is needed to evaluate patient adherence, outcomes and caregiver burden related to twice-daily versus once-daily administration in patients with moderate to severe Alzheimer's disease. A new, once-daily, higher-dose preparation of memantine seems to be well tolerated and may provide additional benefits for selected patients with Alzheimer's disease.