Chronic kidney disease (CKD) has been shown to be associated with high oxidative stress and cardiovascular disease. In this chapter our focus will be on the role of advanced glycation end products (AGE) and their receptor, RAGE in CKD progression and their role on cardiovascular complications. We provide a succinct, yet comprehensive summary of the current knowledge, the challenges and the future therapeutic avenues that are stemming out from novel recent findings. We first briefly review glycation and AGE formation and the role of the kidney in their metabolism. Next, we focus on the RAGE, its signaling and role in oxidative stress. We address the possible role of soluble RAGEs as decoys and the controversy regarding this issue. We then provide the latest information on the specific role of both AGE and RAGE in inflammation and perpetuation of kidney damage in diabetes and in CKD without diabetes, which is the main purpose of the review. Finally, we offer an update on new avenues to target the AGE-RAGE axis in CKD.