Acetylcholinesterase inhibitors (AChEIs) are generally regarded as palliative treatments for Alzheimer’s disease that slow the progression of dementia symptoms without altering Alzheimer’s disease’s underlying pathogenic mechanisms. This concept is based on inference rather than evidence, and has limited the scope and persistence of AChEI use in clinical practice. Recent preclinical studies demonstrate that AChEIs exhibit a number of biological effects in addition to cholinesterase inhibition. A broader understanding of the possible mechanisms of action of AChEIs in Alzheimer’s disease could result in more effective use and assist in the development of new and improved therapies. The available evidence brings into question the prevailing view that AChEIs are exclusively symptomatic treatments and supports the use of these agents persistently throughout the course of Alzheimer’s disease.