Excessive stress gives rise to disturbances in various systems in humans and activates defense mechanisms to maintain homeostasis in the body. Sleep is an essential biological process of which the underlying regulating mechanism involves numerous anatomical structures and biochemical substances that can be compromised by stress and the immune system. Immune sub-stances such as interleukin-1ǰand tumor necrosis factor are related to the homeostatic process of sleep. Interleukin-1ǰinteracts by being involved in an immune regulating feedback chain that activates the hypothalamo-pituitary-adrenal axis which, in turn, is related to the circadian process. Moreover, stress-induced insomnia activates the hypothalamo-pituitary-adrenal axis further to bring about a vicious cycle of stress and insomnia. The pathophysiological theory responsible for chronic insomnia is that of stressdiathesis, which is a series of processes consisting of predisposition, precipitating, and perpetuating factors. In clinical practice, as the process in which stressinduced insomnia passes into a chronic course is directly related to treatment, the understanding of perpetuating factors is indispensable. Sleep disturbance is a very common complaint among pa-tients with posttraumatic stress disorder. Increased noradrenergic activity and REM sleep dysregul-ation seem to have a role in mediating sleep disturbances of this disorder. Sleep disturbance must always be taken into account as an important clinical variable whenever evaluating or managing stress.