The common co-occurrence of kidney and heart disease results from complex mutual pathophysiological mechanisms between the two organs, leads to increased morbidity and mortality, and poses huge therapeutic challenges. As in-depth knowledge of their crosstalk increases, new cardiorenal drugs supported by large, randomized trials are re-defining cardiorenal therapies, bringing cardiorenal medicine into a new era. In this review, we address the shared regulatory mechanisms of cardiorenal interdependence and provide current evidence supporting treatment options around decongestion strategies, renin-angiotensin- aldosterone system inhibitors/angiotensin receptor-neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists. We advocate the inclusion of both renal and cardiac endpoints in pivotal clinical trials of new drugs with cardiorenal effects. Studies investigating the efficacy and safety of combined treatment approaches are needed. Novel approaches to treatment could contribute to optimizing cardiorenal multidisciplinary care, reducing the disease burden, improving clinical outcomes, and contributing to global health.