Alzheimer's disease (AD) is the most common progressive neurodegenerative form of dementia in the elderly and is characterized neuropathologically by neurofibrillary tangles (NFT), amyloid neuritic plaques (NP), and prominent synaptic and eventually neuronal loss. Although the molecular basis of AD is not clearly understood, a neuroinflammatory process, triggered by Abeta42, plays a central role in the neurodegenerative process. This inflammatory process is driven by activated microglia, astrocytes and the induction of proinflammatory molecules and related signaling pathways, leading to both synaptic and neuronal damage as well as further inflammatory cell activation. Epidemiologic data as well as clinical trial evidence suggest that nonsteroidal anti-inflammatory drug (NSAID) use may decrease the incidence of AD, further supporting a role for inflammation in AD pathogenesis. Although the precise molecular and cellular relationship between AD and inflammation remains unclear, interleukins and cytokines might induce activation of signaling pathways leading to futher inflammation and neuronal injury. This chapter will discuss the association between interleukins and neurodegeneration in AD and highlight the significance of genetic and clinical aspects of interleukins in disease expression and progression. As part of an emerging inflammatory signaling network underlying AD pathogenesis, beta-amyloid (Abeta) stimulates the glial and microglial production of interleukins and other cytokines, leading to an ongoing inflammatory cascade and contributing to synaptic dysfunction and loss, and later, neuronal death. Inflammatory pathways involving interleukin and cytokine signaling might suggest potential targets for intervention and influence the development of novel therapies to circumvent synaptic and neuronal dysfunction ultimately leading to AD neurodegeneration.