Coronary artery spasm (CAS) plays an important role in the pathogenesis of ischemic heart disease, including angina pectoris, myocardial infarction, and sudden death, occurring most often from midnight to early morning. CAS is prevalent among East Asians and is associated with an aldehyde dehydrogenase 2 (ALDH2)-deficient genotype (ALDH2*2) and alcohol flushing, which is prevalent among East Asians but is virtually non-existent in other populations. ALDH2 eliminates not only acetaldehyde but also other toxic aldehydes from lipid peroxidation and tobacco smoking, thereby protecting tissues and cells from oxidative damage. Risk factors for CAS include smoking and genetic polymorphisms including those of ALDH2*2, endothelial NO synthase, paraoxonase I, and interleukin-6. Accordingly, oxidative stress, endothelial dysfunction, and low-grade chronic inflammation play an important role in the pathogenesis of CAS, leading to increased coronary smooth muscle Ca2+ sensitivity through RhoA/ROCK activation and resultant hypercontraction. Ca-channel blockers blocking the intracellular entry of Ca2+ are specifically effective for treatment for CAS.