Cyclin-dependent kinases (Cdks) are serine/threonine kinases that regulate a number of cellular processes including the cell cycle and neuronal differentiation. Accumulating evidence indicates that two distinct Cdk pathways may have a role in the neuronal loss that is responsible for Alzheimer's disease. One pathway involves the aberrant reactivation of the cell cycle, a process believed to be incompatible with neuronal function. A second involves dysregulation of Cdk5, a member of this kinase family with no known cell cycle functions, but prominently expressed in postmitotic neurons. Reports supporting the involvement of both pathways are plentiful, but the story is not yet complete. In particular, difficulties incorporating the extended latency of AD into model approaches persist. Despite this, the theory that Cdks are involved in the pathogenesis of AD has generated considerable interest.