Recent published evidence suggests that the correction of the multiple remethylation pathway abnormalities in chronic kidney disease (CKD), beyond folate-related disturbances, enhanced removal of uremic toxins and/or homocysteine (Hcy), and maneuvers aimed to displace Hcy from protein-binding sites, may represent valuable strategies to normalize total Hcy concentrations in CKD patients. The relevance of decreasing Hcy levels for cardiovascular disease in CKD patients should be shown definitively by the results of ongoing randomized trials.