INTRODUCTION In individuals with diabetes, the presence and severity of kidney disease adversely affects their well-being, significantly contributes to burden of morbidity and increases their risk of a premature death. The efficiency of current management strategies for the treatment of diabetic nephropathy, even in optimal combination, is partial, at best. There remains an unmet need for additional renoprotective interventions in patients with diabetes. AREAS COVERED This review presents a comprehensive summary of some of the ?new contenders? for the treatment of diabetic nephropathy that have been tested or are being tested in randomised clinical trials in patients with diabetes with a predefined renal endpoint, but are not currently indicated for renoprotective therapy. Many of these drugs have been in clinical use for other indications, or initially developed for other purposes. EXPERT OPINION Although substantial progress has been made towards understanding the pathogenesis of diabetic nephropathy, at present there are no new drugs that provide the solutions we want for our patients. Even when used in combination with standard medical care, current data indicate that renal complications are at best only modestly reduced, at the expense of additional pill burden and exposure to off-target effects. Given the ever-growing burden of diabetic kidney disease, there is a substantial opportunity for better and more targeted (?smarter?) therapeutic interventions in this context.