Murine models for human autoimmune diseases are an essential tool for studying pathogenesis and for identifying new therapeutic targets. Mice are not the natural disease host, and conventional models have proved to be poor predictors of efficacy and safety in recent trials aiming to translate drug and biologic treatments to humans. Evidently, further steps towards recapitulating human diseases are urgently needed, for example using transgenic predisposing human HLA allele(s) plus T-cell receptor(s) implicated in a representative patient's autoimmune disease. The latest development - humanizing most of the immune system by transplanting human hematopoietic stem cells into severely immunodeficient mice - should lead to even better modeling.