Specific therapies for neurologic diseases such as Alzheimer’s disease provide the potential for better clinical outcomes. Expression of caspases in the brain is developmentally regulated, and dysregulated in neurologic disease, supporting that caspases may be therapeutic targets. The activity of caspases is carefully regulated via binding partners, cleavage, or endogenous inhibitors to prevent spontaneous activation, which could lead to aberrant cell death. This review serves as a brief examination of the current understanding of the regulation and function of caspases, and approaches to specifically target aberrant caspase activity. The use of proper tools to investigate individual caspases is addressed. Moreover, it summarizes the reports of various caspases in Alzheimer’s disease studies. A better understanding of specific caspase pathways in heath and neurodegenerative disease is crucial for identifying specific targets for the development of therapeutic interventions.