Prevention of loss of beta cells in type 1 diabetes is a major goal of current research. Knowledge of the genetic susceptibility, increasing ability to predict who may be at risk, recognition of the potential clinical impact of residual insulin secretion after diagnosis, and development of new immunomodulatory agents have supported an increasing number of clinical trials to prevent beta-cell loss. Interventions can be targeted at 3 stages: before the development of autoimmunity (primary prevention), after autoimmunity is recognized (secondary prevention), or after diagnosis when significant numbers of beta cells remain (tertiary prevention). Thus far, several agents show promise when given shortly after diagnosis, but no interventions before diagnosis have shown benefit. Knowledge in this area has grown quickly in recent years and will continue to grow rapidly with several international collaborative efforts underway.