Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Clinicians, schools, and service agencies worldwide have reported a dramatic increase in the number of children identified with autism. Despite expanding research, the etiology and underlying biological processes of autism remain poorly understood, and the relative contribution from genetic, epigenetic, and environmental factors remains unclear. Although autism affects primarily brain function (especially affect, social functioning, and cognition), it is unknown to what extent other organs and systems are disrupted. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment. A better understanding of the involvement of the immune response in autism, and of how early brain development is altered, may have important therapeutic implications.