Researchers have mapped vascular calcification in chronic kidney disease into five distinct phenotypes, each driven by different molecular mechanisms and uremic toxins. The inflammatory-oxidative phenotype involves indoxyl sulfate and p-cresyl sulfate activating NLRP3 inflammasomes, while the mineral-metabolic phenotype centers on hyperphosphatemia and FGF23 excess. Three additional phenotypes involve epigenetic changes, endocrine disruption, and convergent toxic pathways in advanced disease. This phenotypic classification represents a significant conceptual advance beyond viewing vascular calcification as inevitable mineral deposition. The framework transforms a condition affecting 90% of end-stage kidney patients—and increasing cardiovascular death risk 3-5 fold—into potentially targetable disease subtypes. Each phenotype corresponds to specific biomarker panels and therapeutic approaches, from tissue-nonspecific alkaline phosphatase inhibitors to senolytic agents. This precision medicine approach could revolutionize treatment selection for kidney patients, moving from one-size-fits-all interventions to biomarker-guided therapies. The clinical impact extends beyond nephrology, as cardiovascular complications drive mortality in this population. However, validation through prospective clinical trials remains necessary to confirm whether phenotype-matched treatments improve outcomes compared to standard care.