Purpose of Review <p>The PI3K/Akt/mTOR (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin) signaling pathway is pivotal in regulating cellular functions such as growth, proliferation, survival, and metabolism. Dysregulation of this pathway contributes to the pathogenesis of multiple diseases, including cancer, metabolic disorders, and cardiovascular diseases, notably atherosclerosis. This review outlines the role of the PI3K/Akt/mTOR pathway in the progression of atherosclerosis, emphasizing its involvement in endothelial protection, vascular smooth muscle cell proliferation and migration, as well as inflammatory modulation.</p> Recent Findings <p>The pathway affects atherosclerosis through several mechanisms: it both protects and can harm the blood vessel lining, controls how muscle cells in vessel walls grow, move and die, and influences inflammation. These processes critically affect how plaques form, become unstable, and progress. Current drug treatments and procedures targeting this pathway show promise, though existing therapies often lack specificity.</p> Summary <p>Understanding the many roles the PI3K/Akt/mTOR pathway plays in atherosclerosis offers important insights for creating targeted treatments. While current approaches show potential, we urgently need new interventions that specifically target this pathway to address heart disease complexity and improve patient results. Future studies should focus on developing more precise treatments to effectively reduce atherosclerosis.</p>