Atherosclerosis is the most frequent cause of ischemic heart disease and cerebrovascular disorders. The condition is the leading cause of death in Western societies. At the core of this condition is the atherosclerotic plaque. It is within the structure of this lesion that multiple biochemical and cellular processes interact influencing its vulnerability to rupture and as a result acute ischemic events. This article will discuss the pathophysiology behind the atherosclerotic plaque, particularly those elements that lead to its instability and the medical tools currently available to counteract it.