Type 2 diabetes mellitus is one of the most common disease worldwide. Diabetes mellitus is expected to affect over 380 million people by 2025 and one third of these patients will develop chronic kidney disease (CKD). There are many categories of hypoglycemic agents available for treatment of type 2 diabetes mellitus: sulphounilureas, glinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and the new brand incretines. In nephropatic patients with CKD stage I-II, any hypoglycemic agent can be used: the choice must be linked to a careful evaluation of potential risk and benefit. In CKD stage III to V, conversely, some drugs are not recommended while other agents can be used with dose reduction due to risk of hypoglycemia. In these patients the early use of insulin may be indicated. The target of this review is to evaluate evidences about the possible use of hypoglycemic agents in patients affected by diabetes and CKD stage III-V.