The neurodegenerative disease first described almost 100 years ago by Alois Alzheimer is predicted to be one of the major health problems of the 21st century. Alzheimer's disease (AD) is a progressive dementia characterized by global cognitive decline and is defined pathologically by amyloid plaques and neurofibrillary tangles. Major unmet medical need has encouraged pharmaceutical companies to invest in AD drug development. Promising novel approaches are under way, assisted by recent advances in animal models and an increased understanding of pathophysiology. However, demonstration of disease modification and identification of at-risk individuals are among the significant challenges facing those working in AD drug development.