This review focuses on the methods accessing β-cell function. β-cell failure is the critical step in the development of type 2 diabetes. Therefore, assessment of β-cell function is an important part of the evaluation and treatment of diabetic patients. However, it is not easy because of complex interaction between multiple tissues. Several parameters should be considered, such as glucose level and insulin sensitivity of diverse insulin target tissues to assess β-cell function. To overcome these difficulties, several invasive or non-invasive methods have been developed to assess β-cell function for clinical or research purposes.