It has been almost 15 years since the first report of apoptosis as a major mechanism of cell death associated with Alzheimer's disease (AD). Presently, whether neurons die through apoptosis or some other pathway is still a hotly debated issue. However, mounting evidence suggests a role for the activation of caspases and cleavage of critical cellular proteins during the progression of AD. The activation of apoptotic pathways may represent a protracted battle due to the presence of various anti-apoptotic molecules such as Bcl-2 whereby neurons do not immediately execute the apoptotic program but caspase activation occurs discretely at some low level. During this time, caspase cleavage of the amyloid precursor protein (APP), the adaptor protein GGA3 involved with beta-amyloid production, and tau may promote the formation of beta-amyloid (A beta) and neurofibrillary tangles (NFTs). Thus, not only may activation of caspases represent a terminal event associated with AD (i.e. cell death), but also a proximal event that promotes the pathology underlying this disease. Therefore, therapeutics aimed at preventing the activation and execution of apoptosis may provide an effective means of treating AD.