Atherosclerosis is characterized by chronic inflammation of the vascular wall. Macrophages, which differentiate from circulating monocytes, give rise to foam cells by excessive accumulation of modified lipoproteins. Atherogenesis subsequently progresses through necrotic core expansion associated with apoptosis and the suppressed clearance of apoptotic macrophage (i.e. efferocytosis), followed by the transition to vulnerable plaques. The vulnerable plaque is characterized by thinning of the fibrous cap and necrotic core expansion. Here, the impact of monocytes/macrophages in both early atherogenesis and advanced plaque progression is discussed with a focus on the potential targeting of inflammatory processes in atherosclerosis.