This reprint of the Special Issue "Atherosclerosis 2: From Molecular Mechanisms and Pathophysiology to Novel Therapeutic Approaches" presents recent research exploring vascular health and atherosclerosis. It features a number of original studies, including those of Frolov et al., who used a multi-omics approach to compare endothelial cells from the human coronary artery (HCAEC) and the internal thoracic artery (HITAEC); Dutka et al., who identified osteoprotegerin (OPG) as being crucial for angiotensin II-induced endothelial dysfunction in a mouse model; and Cho et al., who introduced time-averaged wall shear stress standard deviation (WSS) as a new measure of plaque progression. Henni Mansour et al. demonstrated that foam cells generated by oxidized LDL (Mox) are more inflammatory than those generated by acetylated LDL (Mac), while Kathuria et al. identified nidogen-2 (NID2) as a promoter of hepatosteatosis and atherosclerosis in mice through AMPK inhibition. Iusupova et al. discovered that miR-145 predicts ischemia with non-obstructive coronary arteries (INOCA). Sohn and Lim examined the efficacy of cilostazol in reducing MACE, observing a lower risk of bleeding compared to aspirin. Theofilis et al. examined coronary plaque erosion, integrating molecular mechanisms, imaging, and treatment. Kasher et al. examined acetyl glycoproteins (GlycA) as a biomarker linking rheumatoid arthritis inflammation to atherosclerosis. Finally, Getz and Reardon examined the site specificity of atherosclerotic lesion, incorporating genetics, immunity, and perivascular adipose tissue.