Treating Alzheimer's disease (AD) is the biggest unmet medical need in neurology. Current drugs improve symptoms, but do not have profound disease-modifying effects. Three main classes of disease-modification approaches can be defined: one that is broadly neurotrophic or neuroprotective, one that targets specific aspects of AD pathology, and one that is based on epidemiological observation. This review discusses all three approaches, with particular emphasis on anti-amyloid strategies - currently the most active area of investigation. The approaches that are reviewed include secretase inhibition, amyloid-beta aggregation inhibition, immunotherapy and strategies that might indirectly affect the amyloid pathway.