The value of immune monitoring in Type 1 diabetes intervention and prevention studies lies in its potential to identify responders and non-responders to specific therapies. This concept aligns strongly with a common them in translational studies, namely the importance of personalized medicine. At a third level, these ideas would potentially draw support from studies that identify meaningful heterogeneity in the disease. Examples of this might be heterogeneity in immune function, responsiveness to therapy, or pathological findings. Studies conducted in immune interventions and in pathological samples (nPoD) are beginning to provide evidence that supports these concepts. These will be discussed, along with presentation of new findings that include a CD4 phenotypic change associated with clinical response to immune intervention and evidence of polarized functional phenotypes in autoantigen-specific CD4 T cell responses. These findings could lead to assay development that can be used to stratify subjects for relevant intervention and prevention studies.