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Thioredoxin-interacting protein has emerged as a major factor regulating pancreatic β-cell dysfunction and death, key processes in the pathogenesis of type 1 and type 2 diabetes. Accumulating evidence based on basic, preclinical, and retrospective epidemiological research suggests that TXNIP represents a promising therapeutic target for diabetes. The present review is aimed at providing an update regarding these developments.TXNIP has been shown to be induced by glucose and increased in diabetes and to promote β-cell apoptosis, whereas TXNIP deletion protected against diabetes. More recently, TXNIP inhibition has also been found to promote insulin production and glucagon-like peptide 1 signaling via regulation of a microRNA. β-Cell TXNIP expression itself was found to be regulated by hypoglycemic agents, carbohydrate-response-element-binding protein, and cytosolic calcium or the calcium channel blocker, verapamil. Retrospective studies now further suggest that verapamil use might be associated with a lower incidence of type 2 diabetes in humans.TXNIP has emerged as a key factor in the regulation of functional β-cell mass and TXNIP inhibition has shown beneficial effects in a variety of studies. Thus, the inhibition of TXNIP may provide a novel approach to the treatment of diabetes.