Chronic kidney disease (CKD) increases coronary artery disease risk substantially, but is particularly associated with the risk of heart failure and arrhythmias. Consequently, most patients with CKD die from cardiovascular disease (CVD) before progressing to need kidney replacement therapy. The treatment of patients with CKD therefore includes management of CKD-associated CVD risk factors as well as the risk of CKD progression. Meta-analyses have shown that intensively controlling blood pressure and blood glucose reduces the risk of CVD and albuminuria in patients with type 2 diabetes mellitus (DM), and it is presumed—but not demonstrated—that such strategies translate into a reduced risk of kidney failure. Key treatments that placebo-controlled trials have shown to be effective at reducing the risk of both CVD and kidney failure in patients with type 2 DM and CKD target blood pressure and/or intraglomerular hypertension include renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter-2 inhibitors, the nonsteroidal mineralocorticoid receptor antagonist finerenone, and the glucagon-like peptide-1 receptor agonist semaglutide. We recommend prescribing such interventions in combination and early to prevent end-organ damage. Intensive statin-based regimens safely reduce atherosclerotic risk in CKD. Low-dose aspirin is indicated in patients with prior atherothrombotic CVD, but the balance of CVD benefits versus major bleeding risk in those with CKD and DM (but without CVD) is more finely balanced. Reliable randomized evidence that partial correction of dysregulated calcium-phosphate homeostasis (e.g., with 1-alpha hydroxylated vitamin D and phosphate binders) or renal anemia (e.g., with intravenous iron and erythropoiesis-stimulating agents) modifies CVD risk does not exist, but such practices are common.