During the past 20 years, research on Alzheimer disease (AD) and other dementias has increased our understanding of these disorders and has opened doors to new methods of treatment. Acetylcholinesterase inhibitors (AChEIs) have been successful in reducing symptoms in patients with mild-to-moderate AD and led to the US Food and Drug Administration's approval of four AChEIs for the treatment of AD. Although these agents are approved for only mild-to-moderate AD, and the available data for most of them are from trials of only 6 months' duration, long-term studies suggest that the benefits of AChEI treatment can endure for up to 4 years. A common pattern of response to treatment is initial improvement in cognition, followed by maintenance of cognitive gains above baseline for up to 1 year. Generally there is a decline in cognition to below baseline levels after approximately 1 year of treatment, but the level of cognition remains above that predicted for those not receiving pharmacologic treatment. Furthermore, long-term studies suggest that early diagnosis and treatment with AChEIs yield better long-term outcomes. Patients who received continuous pharmacologic treatment from the outset generally had better long-term outcomes than those who received placebo in the double-blind phase of these trials.