Stiffening of the arterial wall is one major mechanism responsible for morbidity and mortality in cardiovascular disease including hypertension and coronary heart disease. Various physiological and pathophysiological parameters influence arterial stiffening including age, gender, blood pressure, nutrition, smoking, and diseases such as hypertension, diabetes, renal failure, and hypercholesterolemia. Thus, assessing arterial stiffness has become a widely used tool to investigate the function of large arteries in epidemiological and clinical studies. Traditionally, arterial stiffness has been assessed by pulse wave velocity, a non-invasive parameter which has been shown to predict cardiovascular mortality. In addition, pulse wave analysis has been increasingly used to determine augmentation index, a parameter that describes the effect of pulse wave reflection on the central aortic pressure configuration. For many years arterial stiffness had been thought to be relatively unaffected by drugs. However, recent studies suggest that arterial stiffness can be pharmacologically modulated. Hence, improving arterial stiffness may be a potential therapeutic target to reduce cardiovascular mortality. This review attempts to summarize the current tools used to assess arterial stiffness and the drugs that modify large artery stiffness in-vivo.