When chronic kidney disease develops, the capacity of the kidneys to clear metabolic waste products from the body is gradually lost. This process results in the retention of a large array of compounds affecting biochemical and biological functions (uremic toxins), of which several can cause cardiovascular damage. This article reviews the main cardiotoxic mechanisms related to uremic toxin retention (endothelial dysfunction, vascular smooth muscle cell alterations, inflammation, mineral bone disorder, insulin resistance, and thrombogenicity) and the main responsible retention compounds. Therapeutic options are reviewed, such as influencing solute generation by intestinal microbiota.