<p>Vascular calcification (VC) is a complex, multifactorial process strongly associated with ageing, atherosclerosis, chronic kidney disease, and diabetes. Despite its clinical significance, effective treatment strategies remain elusive due to an incomplete understanding of the underlying mechanisms. In this review, we critically examine the cellular and molecular pathways that drive VC, including the transdifferentiation of vascular smooth muscle cells (VSMCs), the role of extracellular vesicles, and the influence of oxidative stress and inflammation. We also summarise key inducers and endogenous inhibitors of calcification, highlighting therapeutic targets currently under preclinical or clinical investigation. Notably, we evaluate recent advances in pharmacological and biomaterial-based interventions aimed at halting or reversing calcification, with a focus on their translational potential. By integrating mechanistic insights with therapeutic developments, this review offers a comprehensive perspective on VC pathophysiology and treatment, serving as a timely reference for future research and clinical innovation.</p> Graphical Abstract <p>TOC Figure</p> <p></p>