This review by Michael R. Irwin from the Cousins Center for Psychoneuroimmunology at UCLA highlights the critical role of sleep in promoting health, particularly in relation to the immune system. Sleep disturbances, including insomnia and extreme sleep durations, have been linked to increased risk of infectious diseases, cardiovascular disease, cancer, and depression. The review discusses the biological mechanisms underlying these effects, focusing on the impact of sleep on adaptive and innate immunity. It explores how sleep deprivation and insomnia can alter immune responses, leading to impaired vaccine responses and increased susceptibility to infections. The review also examines the neuroendocrine and autonomic neural pathways that link sleep disturbance to immunity, and the reciprocal links between sleep and inflammatory biology. Finally, it discusses interventions to improve sleep and potential opportunities to promote sleep health for therapeutic control of chronic infectious, inflammatory, and neuropsychiatric diseases.This review by Michael R. Irwin from the Cousins Center for Psychoneuroimmunology at UCLA highlights the critical role of sleep in promoting health, particularly in relation to the immune system. Sleep disturbances, including insomnia and extreme sleep durations, have been linked to increased risk of infectious diseases, cardiovascular disease, cancer, and depression. The review discusses the biological mechanisms underlying these effects, focusing on the impact of sleep on adaptive and innate immunity. It explores how sleep deprivation and insomnia can alter immune responses, leading to impaired vaccine responses and increased susceptibility to infections. The review also examines the neuroendocrine and autonomic neural pathways that link sleep disturbance to immunity, and the reciprocal links between sleep and inflammatory biology. Finally, it discusses interventions to improve sleep and potential opportunities to promote sleep health for therapeutic control of chronic infectious, inflammatory, and neuropsychiatric diseases.