Provision of new beta cells for people with type 1 diabetes has been a quest of biomedical research for over a century, and several important advances have been made in the past 30 years. Successes have been achieved in pancreas and islet transplantation in humans, but each success was accompanied with shortcomings. Therapeutic strategies for the future include protection of transplanted beta cells from drug toxicity and oxidative stress, as well as overcoming supply-demand issues by using human beta cell surrogates, such as immune-protected xenografts and stem cells.