Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder with a complex pathogenesis. Many studies over the last four decades have recognized altered immune responses among individuals diagnosed with ASD. The purpose of this critical and comprehensive review is to examine the hypothesis that immune dysfunction is present more frequently, and it is related to ASD in humans. It was found that that often individuals diagnosed with ASD have alterations in immune cells such as T cells, B cells, monocytes, natural killer cells, and dendritic cells. Also, many individuals diagnosed with ASD have alterations in immunoglobulins and increased autoantibodies. Finally, an important portion of individuals diagnosed with ASD has elevated peripheral cytokines and chemokines and associated neuroinflammation. In conclusion, immune dysregulation and inflammation are important components of ASD diagnosis and are key components of the diagnosis and treatment of ASD.