In diabetes, increasing albuminuria and decreasing glomerular filtration rate are hallmarks of chronic kidney disease in diabetes and increase the risk of atherosclerotic cardiovascular events and mortality as well as the risk for end-stage kidney disease. For two decades, standard of care has been controlling risk factors, such as glucose, blood pressure, lipids, and lifestyle factors, and specifically use of agents blocking the renin-angiotensin system. This has improved outcome, but a large unmet need has been obvious. After many failed attempts to advance the therapeutic options, the past few years have provided several new promising treatment options such as sodium–glucose cotransporter 2 inhibitors, endothelin receptor antagonists, glucagon-like peptide 1 agonists, and nonsteroidal mineralocorticoid receptor antagonists. The benefits and side effects of these agents demonstrate the link between kidney and heart; some have beneficial effects on both, whereas for other potentially renoprotective agents, development of heart failure has been a limiting factor. They work on different pathways such as hemodynamic, metabolic, inflammatory, and fibrotic targets. We propose that treatment may be personalized if biomarkers or physiological investigations assessing activity in these pathways are applied. This could potentially pave the way for precision medicine, where treatment is optimized for maximal benefit and minimal adverse outcomes. At least it may help prioritizing agents for an individual subject.