Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, with atherosclerosis as a central pathological process driven by lipid imbalances. Apolipoproteins A (apoA) and B (apoB) are key regulators of lipid metabolism and atherogenesis, representing protective and pro-atherogenic roles, respectively. ApoA, primarily found in high-density lipoproteins (HDL), facilitates reverse cholesterol transport and exhibits anti-inflammatory and antioxidant properties, thereby reducing cardiovascular risk. In contrast, apoB, a major component of low-density lipoproteins (LDL) and other atherogenic lipoproteins, promotes cholesterol deposition and plaque formation within arterial walls. This article reviews the metabolic pathways of apoA and apoB, elucidates their opposing roles in the initiation and progression of atherosclerotic plaques, and highlights their clinical utility as biomarkers. The apoB/apoA-I ratio emerges as a superior predictor of cardiovascular risk compared to traditional lipid measures, enabling improved risk stratification and personalized management. Advancements in apoB quantification and the therapeutic potential of targeting apolipoproteins underscore their importance in future strategies to prevent and treat CVDs globally.