Although there has been tremendous improvement in managing chronic kidney disease (CKD) with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in the last 15 years, CKD still progresses. Therefore, new emerging strategies are needed. The gold standard still lies with optimum renin-angiotensin-aldosterone system blockade, although many questions remain about how this is best achieved, such as regarding the efficacy of combinations of ACE inhibitor and ARBs, supramaximal doses of ARBs alone and combinations of either ACE inhibitor or ARBs with direct renin inhibitors, antialdosterone agents. Other promising molecules currently being tested are endothelin receptor antagonists and glitazones. Also, the role of other current therapies being used during CKD, including statins, vitamin D and erythropoiesis-stimulating agents, will be discussed, as these may also exert nephroprotective effects.