Heritable connective tissue diseases comprise a heterogeneous group of multisystemic disorders that are characterized by significant morbidity and mortality. These disorders do not merely result from defects in the amount or structure of one of the components of the extracellular matrix, as the extracellular matrix also serves other functions, including sequestration of cytokines, such as transforming growth factor beta (TGFβ). Indeed, disturbed TGFβ signaling was demonstrated in several heritable connective tissue diseases, including syndromic forms such as Marfan or Loeys-Dietz syndrome and non-syndromic presentations of thoracic aortic aneurysm/dissection. Because of these findings, new therapeutic targets have been unveiled, leading to the initiation of large clinical trials with angiotensin II type 1 receptor antagonists that also have an inhibiting effect on TGFβ signaling. Here, we present an overview of the clinical characteristics, the molecular findings, and the therapeutic strategies for the currently known syndromic and non-syndromic forms of thoracic aortic aneurysm/dissection.