The different forms of diabetes mellitus differ in their pathogenesis but, ultimately, they are all characterized by progressive islet β‐cell loss. Restoring the β‐cell mass is therefore a major goal for future therapeutic approaches. The number of β‐cells found at birth is determined by proliferation and differentiation of pancreatic progenitor cells, and it has been considered to remain mostly unchanged throughout adult life. Recent studies in mice have revealed an unexpected plasticity in islet endocrine cells in response to stress; under certain conditions, islet non‐β‐cells have the potential to reprogram into insulin producers, thus contributing to restore the β‐cell mass. Here, we discuss the latest findings on pancreas and islet cell plasticity upon physiological, pathological and experimental conditions of stress. Understanding the mechanisms involved in cell reprogramming in these models will allow the development of new strategies for the treatment of diabetes, by exploiting the intrinsic regeneration capacity of the pancreas.