Alzheimer's disease is an ever-increasing health concern among the aging population, and as we research new and existing treatments for this disease we begin to uncover possibilities for its prevention. Observational studies and animal models have provided promising findings and generated excitement, but placebo-controlled clinical trials are required to demonstrate true efficacy for these treatments.In the past two decades, clinical trials have led to the approval of symptomatic treatments for Alzheimer's disease, including cholinesterase inhibitors and, more recently, an NMDA receptor antagonist. Clinical trials have also examined antioxidants, NSAIDs, hormone replacement, nutritional supplements and nonpharmacological interventions for the treatment and prevention of Alzheimer's disease. While the results of many of these trials have been disappointing, new mechanisms targeting the hallmark pathology of Alzheimer's disease are currently under investigation, including immunotherapy and secretase modulation, targeted at reducing the amyloid burden, for which we await the results. We review the evidence from completed trials, support for ongoing studies and propose directions for future research.