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Epidemiological studies have shown that ageing is a major non-reversible risk factor for cardiovascular disease. Vascular ageing starts early in life and is characterized by a gradual change of vascular structure and function resulting in increased arterial stiffening. At the present review we discuss the role of the most important molecular pathways involved in vascular ageing, their association with arterial stiffening and possible novel therapeutic targets that may delay this otherwise irreversible degenerating process. Specifically, we discuss the role of oxidative stress, telomere shortening, and ubiquitin proteasome system in endothelial cell senescence and dysfunction in vascular inflammation and in arterial stiffening. Further, we summarize the most important molecular mechanisms regulating vascular ageing including sirtuin 1, telomerase, klotho, JunD, and amyloid beta 1–40 peptide.Vascular ageing starts early in life and is characterized by vascular changes resulting in increased arterial stiffening.Arterial stiffness is the hallmark of vascular ageing.Specific molecular pathways have been identified that lead to vascular ageing.These molecular pathways may be targeted to possibly delay the progression and adverse outcomes of vascular ageing.