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This chapter describes the syndromes of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Many elderly persons exhibit MCI, characterized by memory complaints and mild abnormalities of performance on formal tests, associated with intact general cognition and preserved activities of daily living. The clinical manifestations of AD arise from abnormalities involving brain regions and neural circuits composed of populations of neurons that are essential for memory, learning, and cognitive performance. Early information about the involvement of neurotransmitter-specific circuits damaged by the disease led to the design of early therapies for AD. The genetics of AD are complex, often influencing phenotype in an age-dependent manner. Late onset cases of AD without clear familial association reflect the influences of a variety of risk factors. The chapter emphasizes the need for safe and effective mechanism-based therapies for AD. New treatments will probably require combinatorial approaches.