Book excerpt: Major psychiatric disorders, including schizophrenia, bipolar disorder and major depression represent complex phenotypes with imprecise diagnostic boundaries. It has been found that these disorders can be characterized by a number of peripheral immune-inflammatory alterations, including, i.e. elevated levels of pro-inflammatory cytokines, increased levels of specific and non-specific antibodies or abnormal counts of lymphocyte subpopulations. Although it has been found that major psychiatric disorders share similar dysregulations of immune-inflammatory response, recent studies have also clearly demonstrated that some differences can be indicated. Interestingly, certain immune-inflammatory disturbances appear to be state markers, since they occur in acute relapse and normalize following pharmacological treatment, while the rest represents trait markers that remain stable regardless of treatment. It is also important to note that peripheral immune-inflammatory markers have been associated with psychopathological manifestation of major psychiatric disorders, response to treatment and long-term outcomes. However, it remains unclear what is the origin of peripheral inflammation in psychiatric disorders. To date, several mechanisms have been proposed, including the gut-brain axis dysregulation, infections in the neurodevelopmental period or immunogenetic factors. This eBook summarizes current evidence from studies investigating peripheral inflammation in schizophrenia, bipolar disorder, major depression and post-traumatic stress disorder as well as it provides future directions for the field.