Adequate sleep is an important part of a healthy and productive lifestyle. However, chronic sleep restriction is very common. American adults only sleep an average of 6.85 hours per night. Furthermore, only 37% of Americans report taking more than 8 hours of sleep each night, and 31% of adults report sleeping less than 6 hours per night. Competing priorities including long work hours, family needs, and increased 24-hour access to visual media play a role in this deficit of sleep. It has been shown that sleep restriction and disruption can result in excessive daytime sleepiness and reduced neurocognitive function. More recently, it has been demonstrated that this degree of sleep loss may have long-term health consequences and is associated with premature death, cardiovascular disease, the development of diabetes, and cancer. The health consequences are postulated to be due to disruptions in sleep and changes in circadian rhythms, perhaps under the direction of inflammation and immune mediators. This chapter will explore the recent developments in understanding the interactions between sleep, biological rhythms, the immune systems and their consequences for both health and disease. We will begin by examining studies which evaluate the behavioral and physiological consequences of sleep deprivation. Then we will explore the possible link between these observations and inflammation and immune regulation. Finally, we will look at the potential contribution of these disruptions to disease.