Thoracic aortic aneurysms (TAA) increase the risk of aortic dissection or rupture and represent an important source of morbidity and mortality. Inherited forms of the disease, including Marfan syndrome, have been recognized for a long time but were considered degenerative diseases characterized by cystic medial necrosis of the aortic wall. Improved definition of the structure and function of the normal aortic wall, coupled with the discovery of genetic mutations in key regulatory molecules, have contributed to a more detailed understanding of the pathophysiology of syndromic, familial and sporadic TAAs. We here review the cellular and molecular mechanisms involved in TAA formation and outline areas for future research.