Monogenic diabetes is a type of diabetes characterized by single gene mutation. Due to its heterogeneity and overlap with type 1 and type 2 diabetes, it is difficult to be accurately diagnosed clinically. Correct diagnosis is essential for certain types of monogenic diabetes, however, there is still a lack of simple clinical criteria for selecting patients for genetic testing or even interpreting the results of genetic testing. The classification of monogenic diabetes (including maturity onset diabetes of the young, neonatal diabetes mellitus, mitochondrial diabetes mellitus and syndromic diabetes mellitus) and the clinical diagnosis and corresponding treatment methods of monogenic diabetes based on the new generation sequencing and clinical characteristics have been reviewed in present paper for providing theoretical basis for clinical diagnosis of physicians as well as help to individualize the treatment of patients with monogenic diabetes.