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Drug safety and tolerability is paramount in maximising efficacy and optimising patient and carer quality of life, as patients are vulnerable to adverse events (AEs) and\/or compliance difficulties. The two principal categories of drug used in the treatment of AD are the acetylcholinesterase inhibitors (AChEIs) and the NMDA\u2010receptor antagonist, memantine. This paper reviews the most recent safety data for memantine in comparison with the AChEIs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Review of most recent safety\/tolerability data for memantine and AChEIs, derived from meta\u2010analyses, pooled analyses, European SPCs and EMEA publications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Memantine was found to have a favourable tolerability profile when used as monotherapy or in combination with other agents. AChEIs were found to be fairly well tolerated. All treatments commonly or very commonly produce dizziness and\/or headache. AChEIs are associated with many more types of AEs than memantine, particularly in the gastrointestinal category. Agitation is a less common AE when comparing memantine treatment to placebo, but just as common when comparing AChEI treatment to placebo. Withdrawals in memantine\u2010treated groups are comparable to placebo, and more common in AChEI\u2010treated groups compared to placebo. Overall, drug\u2013drug interactions, contraindications and warnings were fewer for memantine than AChEIs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In both the clinical and naturalistic setting, memantine displays a safety and tolerability profile that is favourable and distinct from that of AChEIs. Safety and tolerability profiles should be given careful consideration when selecting treatment for AD patients. 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