Although enormous progress has been made in the prevention and treatment of cardiovascular disease, it still remains the leading cause of death worldwide. During the last decades, advances in the understanding of the pathophysiology of vulnerable plaque progression, coupled with novel diagnostic and therapeutic approaches, created a new opportunity for progress against cardiovascular disease. It has been demonstrated that inflammation, implicated in all stages of atherosclerosis, is an integral part of vulnerable plaque development and progression, leading eventually to plaque instability. Thus, new diagnostic modalities have been proposed for the detection of local plaque inflammation. Moreover, treatments such as stenting, photodynamic therapy, and novel pharmaceutical agents are under consideration as methods to stabilize the vulnerable plaques by inhibiting inflammation. This review provides an overview of the inflammatory process leading to atherosclerotic cardiovascular disease and the potential clinical strategies that may substantially decrease the incidence of events. We will mention the major impact of local and systemic inflammation on plaque advancing and destabilization, the imaging techniques for early detection of vulnerable plaques and the potential therapeutic strategies.