Diabetes mellitus represents a global health concern, which is expected to worsen over the years. The prevalence is estimated to increase up to 642 million people by 2040. Almost half of diabetic patients are at a high risk of developing kidney involvement up to dialysis; moreover, macrovascular complication could be an obstacle to kidney transplant. Besides the classic albuminuric phenotype, non-albuminuric diabetic kidney disease was also discovered recently. Fortunately, compared with classic therapy with diet, oral hypoglycemic drugs, and insulin, current clinicians can rely on several new drugs that act with different pathways characterized by kidney and heart protection, as shown by several clinical trials and confirmed in clinical practice. Herein, we will review the therapies that nephrologist and diabetologist have available today and the future perspective.