The purpose of this review is to summarize currently available evidence implicating vitamin K in the pathogenesis of vascular calcification (VC), in particular arterial medial calcification. In doing so, we try to provide a rationale for an interventional clinical study testing whether vitamin K supplementation can retard VC or even affect cardiovascular mortality in chronic kidney disease patients. Additionally, we wish to give an overview of the current literature indicating potential adverse effects of long-term vitamin K antagonists in this population.