Alzheimer's disease (AD) is the most common neurodegenerative disease and seriously damages the health of elderly population. Clinical drug research targeting at classic pathology hallmarks, such as amyloid- (A) and tau protein, failed to achieve effective cognitive improvement, suggesting that the pathogenesis of AD is much complicated, and there are still other unknown and undetermined important factors. Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin-dependent serine/threonine kinase that plays an important role in various neuronal injury models. Mounting evidence has demonstrated that DAPK1 variants are associated with AD risk. The activation of DAPK1 is also involved in AD-related neurodegeneration in the brain. Exploring the roles of DAPK1 in AD might help us understand the pathogenic mechanisms and find a novel promising therapeutic target in AD. Therefore, in this review, we comprehensively summary the main progress of DAPK1 in the AD studies from genetic risk, neuropathological process, and clinical potential implications.