Despite its high worldwide prevalence and the intuitable negative prognostic connotation, for a long time peripheral artery disease (PAD) has not been the subject of particular interest by the cardiac scientific community. The availability of a new therapeutic strategy (low-dose rivaroxaban associated with acetylsalicylic acid) has reignited interest in PAD. The clear evidence derived from the COMPASS and VOYAGER PAD trials, with the possibility of using dual pathway inhibition, has given new energy to the therapeutic front against symptomatic PAD also associated with coronary artery disease. This review article aims to revisit the pathophysiological concepts underlying PAD and the path of the various clinical trials that have led to new scientific evidence.