<p>The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data. In addition, large randomized clinical trials have demonstrated the effectiveness of sodium–glucose co-transporter 2 inhibitors, glucagon-like peptide&#xa0;1 receptor agonists and mineralocorticoid receptor antagonists in reducing adverse events in CKD, greatly expanding the options for effective therapy. Alongside angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, these classes of medication have been proposed to be the four pillars of CKD pharmacotherapy. However, all of these drug classes are underutilized, even in individuals at high risk. Leveraging prognostic estimates to guide therapy could help clinicians to prescribe CKD-related therapies to those who are most likely to benefit from their use. Risk-based CKD management thus aligns patient risk and care, allowing the prioritization of absolute benefit in determining therapeutic selection and timing. Here, we discuss CKD prognosis tools, evidence-based management and prognosis-guided therapies.</p>