Autoimmune diseases are complex and heterogeneous in nature and show varying responses to therapeutic treatment. A more accurate biological characterization of individual patients would assist in disease classification, prognosis, and treatment decisions. This characterization ideally would incorporate cellular, biochemical, and molecular information that contribute to the inflammatory state. The advent of single-cell network profiling (SCNP) using phospho-flow multiparametric flow cytometry allows insight into the complexity of signaling networks in various cell types. Here, we describe the potential of SCNP to inform on the biological characterization of autoimmune disease, the application in clinical medicine, and the utility in drug development.