Patients with type 1 diabetes (T1D) rapidly lose β cell function and/or mass, leading to a life-long dependence on insulin therapy. β Cell destruction is mediated by aberrant immune responses; therefore, immune modulation has potential to ameliorate disease. While immune intervention in animal models of diabetes has shown promising results, treatment of patients with T1D with the same agents has not been as successful. In this issue of the JCI, Haller and colleagues present data from a small clinical trial that tested the efficacy of a combination of immunomodulatory agents, anti-thymocyte globulin and pegylated granulocyte CSF, neither of which have shown benefit for T1D as single treatment agents. Many patients that received combination therapy maintained β cell function at baseline levels up to a year after treatment. The results from this study challenge current trial design paradigm that for combined therapy to be successful individual agents should show benefit.