The prevalence of chronic kidney disease in patients with diabetes continues to increase. Management of these patients is quite challenging, as it needs a comprehensive and personalized approach, in line with the available studies and guidelines proposing individualized glycemic targets. The cornerstone of optimal glycemic control starts with the knowledge of the pharmacokinetics and pharmacodynamics of the available antihyperglycemic medications combined with the data from outcomes studies to help us understand the risks and benefits of these therapies for this specific subset of patients. In this chapter, we will review the latest evidence guiding optimal glycemic control in patients with chronic kidney disease. We will focus on currently available antihyperglycemic agents including their limitations in these subset of patients, glycemic targets, monitoring glycemic control, and the importance of comprehensive multidisciplinary care for diabetic patients with chronic kidney disease. We will also highlight the fact that normoglycemia needs to be maintained safely and discuss the impact of hypoglycemia in this chapter as it relates to patients with chronic kidney disease.