While much of the Alzheimer's disease (AD) research community turns its spotlight on genetics, molecular biology, and the neurotoxicity of beta-amyloid, there is a more subtle but equally significant shift in focus emerging within AD therapeutic circles. Once devoid of specific treatment options, the field now enjoys a choice of two Food and Drug Administration (FDA)-approved cholinesterase inhibitors and the prospect of several more in the near future. In addition, therapy for AD is rapidly expanding beyond the central cholinergic hypothesis to include neuroprotective agents and the possibility of interfering with basic mechanisms involved in the pathogenesis of this disorder. Clinically, we have entered the era of viable cholinergic therapies, and we are already moving beyond that starting point to an era of effective combination approaches. This article provides a clinical framework for these current and potential new therapies.