A large body of evidence has helped reframe atherosclerotic cardiovascular disease from a mere lipid storage disorder to a chronic inflammatory disease. Both innate and adaptive immune pathways contribute to atherogenesis, plaque progression, and plaque destabilization. Macrophages, T cells, and cytokines-among them IL-1β, IL-6, and IL-18-have emerged as key immune cells and mediators implicated in atherosclerosis progression. Residual inflammatory risk-as measured by highly sensitive C-reactive protein (hsCRP) - has gained broad clinical acceptance as an important biomarker of cardiovascular risk prediction independent of cholesterol burden. Finding strategies that target residual inflammatory risk has proven an elusive goal in preventative cardiology. Specific approaches-such as IL-1β inhibition or low-dose colchicine-have shown benefit in reducing cardiovascular events, while other strategies have failed, underscoring the importance of targeting disease-relevant immune pathways and selecting patients that will benefit. Newer approaches-including IL-6 inhibitors, NLRP3 inflammasome inhibitors, and low-dose IL-2-offer promise for further risk reduction. Efforts to use inflammatory biomarkers to more precisely identify patients who may benefit may further improve the benefit-to-risk profile of emerging therapies.