A hallmark of autoimmune diseases is the production of high titers of highly specific autoantibodies, which are routinely measured to guide clinical decision-making. Multiplex antigen microarrays are powerful tools that can provide profiles of the autoantibodies found in blood and other biological fluids. This high-throughput technology allows for rapid identification of antibody and antigen biomarker sets, which is sorely needed in the clinic to improve diagnosis, predictions of prognosis, and selection of targeted therapies. In this article we will describe the antigen microarray technologies that are currently available, and those that are in development. We highlight recent applications for antibody profiling, as well as the challenges that need to be faced before such technologies enter the clinic.