Over the last decade, our knowledge of β-cell biology has expanded with the use of new scientific techniques and strategies. Growth factors, hormones and small molecules have been shown to enhance β-cell proliferation and function. Stem cell technology and research into the developmental biology of the pancreas have yielded new methods for in vivo and in vitro regeneration of β cells from stem cells and endogenous progenitors as well as transdifferentiation of non-β cells. Novel pharmacological approaches have been developed to preserve and enhance β-cell function. Strategies to increase expression of insulin gene transcription factors in dysfunctional and immature β cells have ameliorated these impairments. Hence, we suggest that strategies to minimize β-cell loss and to increase their function and regeneration will ultimately lead to therapy for both Type 1 and 2 diabetes.