Atherosclerosis progression is associated with a complex array of cellular processes in the arterial wall, including endothelial cell activation/dysfunction, chemokine-driven recruitment of immune cells, differentiation of monocytes to macrophages and their subsequent transformation into lipid laden foam cells, activation of inflammasome and pro-inflammatory signaling, and migration of smooth muscle cells from the media to the intima. The use of in vitro model systems has considerably advanced our understanding of these atherosclerosis-associated processes and they are also often used in drug discovery and other screening platforms. This chapter will describe key in vitro model systems employed frequently in atherosclerosis research.