A challenge in the pancreatic β-cell field has been to identify a promoter fragment that is active only in the β-cell compartment and inactive in other regions, such as the hypothalamic region of the brain. The presence of Cre recombinase alone in some models may also affect glucoregulation, confounding interpretation of gene function in the β-cell. A paper presented within describes the development and characterization of 2 new transgenic mice expressing Cre recombinase under the mouse insulin1 promoter that are useful for β-cell-specific gene ablation: the first is constitutive and coexpresses DsRed (Ins1-Cre-DsRed); the second allows β-cell-specific expression of the reverse tetracycline-controlled transactivator, which can be used for drug-dependent expression of a target gene of interest for overexpression studies. These novel models show robust specificity and efficiency and will be valuable tools for functional studies of gene action in β-cells, potentially alleviating current issues associated with previously available mouse lines.