The most common cause of kidney failure in the United States and across the world is diabetes mellitus (DM). Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in persons with diabetes, and chronic kidney disease (CKD) further increases overall CVD risk. It is important to individualize glycemic targets for patients to maintain glucose levels that will reduce the development and progression of complications while avoiding hypoglycemia. CKD alters the relationship of glucose levels to measures of long-term control, such as hemoglobin A1c. Medications used to treat DM may need dose adjustments as CKD progresses. Some medications have particular characteristics in patients with CKD. Insulin and sulfonylureas increase the risk of hypoglycemia, some glucagon-like peptide 1 receptor agonists reduce the risk of CVD outcomes, and most sodium/glucose cotransporter 2 inhibitors reduce the risk of CKD and CVD outcomes. Therefore, for the individual patient, changes in medication types and doses may need constant attention as CKD progresses. Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.