Atherosclerosis is an inflammatory disorder that can evolve into an acute clinical event by plaque development, rupture, and thrombosis. Plaque vulnerability represents the susceptibility of a plaque to rupture and to result in an acute cardiovascular event. Nevertheless, plaque vulnerability is not an established medical diagnosis, but rather an evolving concept that has gained attention to improve risk prediction. The availability of high-resolution imaging modalities has significantly facilitated the possibility of performing in vivo regression studies and documenting serial changes in plaque stability. This review summarizes the currently available non-invasive methods to identify vulnerable plaques and to evaluate the effects of the current cardiovascular treatments on plaque evolution.