Mast cells (MCs) regulate inflammation and immunity. Their granular content includes heparin, histamine, and several enzymes (tryptase, chymase, carboxypeptidase, and cathepsin G). In addition, activated MCs synthesize and release eicosanoids and a large number of cytokines and chemokines. Recent findings suggest a role of MCs in abdominal aortic aneurysms (AAAs) in humans, where they are found in the media and adventitia. Experimentally induced AAA in MC-deficient animals and animals treated with MC inhibitors demonstrate that MCs are involved in the pathogenesis of AAA via several different mechanisms. MC-dependent activation of metalloproteinases and the renin-angiotensin system, contribution to smooth muscle cell apoptosis, and release of proteolytic enzymes are some key examples. Human studies indicate that MCs are the main source of cathepsin G in AAAs and contribute to activation of the renin-angiotensin system via chymase and cathepsin G. Activated MCs also contribute to neovascularization, inflammation, and atherosclerosis, all hallmarks of AAA. Thus, we may envision that MC stabilizing agents, as well as leukotriene receptor antagonists and histamine receptor blockers already in clinical use for treatment of other diseases, could also be tested for their efficacy in preventing development and growth of AAA.