There is extensive bi-directional communication between the brain and the immune system in both health and disease. In recent years, the role of an altered immune system in the etiology of major psychiatric disorders has become more apparent. Studies have demonstrated that some patients with major psychiatric disorders exhibit characteristic signs of immune dysregulation and that this may be a common pathophysiological mechanism that underlies the development and progression of these disorders. Furthermore, many psychiatric disorders are also often accompanied by chronic medical conditions related to immune dysfunction such as autoimmune diseases, diabetes and atherosclerosis. One of the major psychiatric disorders that has been associated with an altered immune system is schizophrenia, with approximately one third of patients with this disorder showing immunological abnormalities such as an altered cytokine profile in serum and cerebrospinal fluid. An altered cytokine profile is also found in a proportion of patients with major depressive disorder and is thought to be potentially related to the pathophysiology of this disorder. Emerging evidence suggests that altered immune parameters may also be implicated in the neurobiological etiology of autism spectrum disorders. Further support for a role of immune dysregulation in the pathophysiology of these psychiatric disorders comes from studies showing the immunomodulating effects of antipsychotics and antidepressants, and the mood altering effects of anti-inflammatory therapies. This review will not attempt to discuss all of the psychiatric disorders that have been associated with an augmented immune system, but will instead focus on several key disorders where dysregulation of this system has been implicated in their pathophysiology including depression, schizophrenia and autism spectrum disorder.