Inflammation is considered an important aspect in the development of atherosclerosis. Genetic manipulations of animal models susceptible to atherosclerosis have unraveled the contribution of various inflammatory pathways implicated in the development of atherosclerosis. These inflammatory pathways not only lead to the recruitment and entry of inflammatory cells into the arterial wall, they also modify the morphology and composition of atherosclerotic plaques. Certain inflammatory pathways, such as P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, appear to play an important role in lesion initiation, whereas others, such as interleukin-10 and CD40/CD40 ligand, seem to contribute to lesion progression and morphologic changes. An understanding of these pathways will allow the development of new strategies in the management of atherosclerosis. This review provides a roadmap for better utilization of these models in atherosclerosis research.