There is evidence that many diseases are accompanied by immunological perturbations and even when the perturbations are not directly pathogenic, they can provide correlative signatures of pathology that can be useful diagnostically. For example, the neuromuscular disease, multiple sclerosis, has a pathophysiology that is immunologically mediated, evinced by the use of increasingly sophisticated immunosuppression therapy and by animal studies in which many of the symptoms can be reproduced by breaking immunological tolerance to myelin basic protein. By contrast, immunological correlates exist for other diseases, such as schizophrenia, but it is not clear which, if any, are causative. The problem is compounded in that genome-wide association studies have shown strong genetic correlation between schizophrenia and bipolar disorder, moderate correlation with schizophrenia and major depressive disease, and low correlation with autism spectrum disorders, yet schizophrenia and autism spectrum disorders share immunological signatures. This example illustrates the problem of ferreting out specific, and hopefully causal, immunological correlates with schizophrenia that differentiate it from genetically or immunologically related psychiatric disorders. Fortunately, recent advances in systems immunology provide potent tools to tackle this problem. This review will illustrate these tools by recent examples and sketch out possible pathways to use them for identification of schizophrenia-specific immunological correlates.