Proteinuria has been strongly correlated with reduced function and graft survival in kidney-transplanted patients. Data regarding new strategies in proteinuria treatment and subsequent allograft survival are lacking. Similarities between chronic graft injury and chronic kidney disease (CKD) suggest that the same therapeutic antiproteinuric tools should be effective in kidney-transplanted patients. The classic strategies to decrease proteinuria such as blood pressure control, nicotine cessation, low-salt diet, and maintaining an ideal body weight seem to be not enough to achieve proteinuria control. Improvements in our understanding of the pathogenesis of CKD have led to the identification of several novel targets for proteinuria management. In this review, we discuss novel pharmacological approaches that aim to decrease proteinuria in CKD patients, including the use of direct renin inhibitors, vitamin D analogs, pentoxifylline, and endothelin receptor antagonists. We also discuss the promise of using antifibrotic agents to treat proteinuria. The identification of new biomarkers of CKD and its progression can help in the selection of the most effective treatment for decreasing proteinuria and maintaining kidney function.