Background: Autoantibodies targeted against a variety of self-antigens are detected in autoimmune diseases and cancer. Emerging evidence has suggested the involvement of environmental factors such as infections and xenobiotics, and some dietary proteins and their antibodies in the pathogenesis of many autoimmune diseases. These antibodies appear in the blood years before presentation of symptoms in various disorders. Therefore, these antibodies may be used as biomarkers for early detection of various diseases. Objective: To provide an overview of antibody arrays that are measured against different human tissue antigens, crossreactive epitopes of infectious agents, dietary proteins, and haptenic chemicals in autoimmune diseases and cancer. Method: Microarray analysis of antigen-antibody reaction. Conclusion: The application of these antibody arrays to human autoimmune disease is expanding and is allowing for the identification of patterns or antibody signatures, thus establishing the premises for increased sensitivity and specificity of prediction, as well as positive predictive values. The presence of these antibodies would not necessarily mean that a patient would definitely become sick but may give a percentage of risk for different conditions that may develop over future months or years. Using this high-throughput microarray method, it is possible to screen rapidly for dozens of autoantibodies at low cost. This is an important factor in the implementation of autoantibody testing as a routine part of medical examinations.