Diabetes mellitus (DM) is a leading cause of chronic kidney disease (CKD) and a major source of morbidity and mortality in patients with established CKD. Loss of kidney function and dialytic therapies conspire to change glycemic regulation in ways that can both worsen and improve blood glucose control. Despite the unique nature of DM in patients with CKD, there currently are no specific guidelines to direct glycemic therapy in these patients. There is benefit of glycemic therapy in preventing such complications as diabetic kidney disease and mortality in patients with no kidney disease, but such benefits are largely unproven in patients with advanced CKD. By reviewing the relevant literature, we argue that glycemic control can still be beneficial in preventing complications, even in dialysis-dependent patients, but there is need for a much better understanding of the CKD-related characteristics of DM. More research is needed to determine whether uremia-related improvement in glycemic control can have a beneficial impact. Finally, we are at an important crossroads in the development of several novel therapeutic agents against diabetic kidney disease. We provide an overview of such agents and their stage of development.