CKD is a major public health problem. It is characterized by a multitude of risk factors that, when aggregated, can strongly modify outcome. While major risk factors, namely, albuminuria and low estimated glomerular filtration rate (eGFR) have been well analyzed, a large variability in disease progression still remains. This happens because (1) the weight of each risk factor varies between populations (general population or CKD cohort), countries, and single individuals and (2) response to nephroprotective drugs is so heterogeneous that a non-negligible part of patients maintains a high cardiorenal risk despite optimal treatment. Precision nephrology aims at individualizing cardiorenal prognosis and therapy. The purpose of this review is to focus on the risk stratification in different areas, such as clinical practice, population research, and interventional trials, and to describe the strategies used in observational or experimental studies to afford individual-level evidence. The future of precision nephrology is also addressed. Observational studies can in fact provide more adequate findings by collecting more information on risk factors and building risk prediction models that can be applied to each individual in a reliable fashion. Similarly, new clinical trial designs can reduce the individual variability in response to treatment and improve individual outcomes.© 2020 S. Karger AG, Basel.