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The kidney is probably the most important target of microvascular damage in diabetes. A significant proportion of people with diabetes develop kidney disease because of their disease and/or other comorbidities, including hypertension and age-related kidney loss. The presence and severity of chronic kidney disease (CKD) identifies individuals at increased risk for adverse health outcomes and premature mortality. Therefore, the prevention and treatment of CKD in diabetics is now a central goal of their general care. Intensive care of diabetic patients includes blood sugar and blood pressure control and blockade of the renin-angiotensin-aldosterone system; these approaches reduce the incidence of diabetic kidney disease and slow its progression. In fact, the significant reduction in the incidence of diabetic kidney disease (DKD) over the past 30 years and the improvement in patient prognosis is largely due to improvements in diabetes management. However, there is a need for innovative treatment strategies to prevent and control the progression of DKD. In this review, we summarize what is currently known about the pathogenesis of CKD in patients with diabetes and the key pathways and targets involved in its progression. In addition, we discuss the current evidence that supports the prevention and treatment of DKD and some of the controversies. Finally, we will explore ways to develop new interventions by making urgently needed investments in targeted and focused research.