Pro-inflammatory cytokines coordinate immune, physiological, metabolic and behavioral responses that are collectively termed the acute phase reaction. In addition to their role in immunoregulation of inflammatory processes, pro-inflammatory cytokines represent the major communication link between peripheral immunity and the central nervous system. Studies in animals have demonstrated that acute activation of pro-inflammatory cytokine signaling in the brain in response to peripheral immune activation is associated with deficits in hippocampal-dependent memory. This book presents and discusses human and animal models studies of the role of cytokines in learning and memory.