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Despite recent advances, insulin therapy remains a treatment, not a cure, for diabetes mellitus with persistent risk of glycaemic alterations and life‐threatening complications. Restoration of the endogenous β‐cell mass through regeneration or transplantation offers an attractive alternative. Unfortunately, signals that drive β‐cell regeneration remain enigmatic and β‐cell replacement therapy still faces major hurdles that prevent its widespread application. Co‐transplantation of accessory non‐islet cells with islet cells has been shown to improve the outcome of experimental islet transplantation. This review will highlight current travails in β‐cell therapy and focuses on the potential benefits of accessory cells for islet transplantation in diabetes.