The natural history of an abdominal aortic aneurysm (AAA) is of progressive aortic wall degeneration occurring over the course of many years, ultimately, culminating in loss of structural integrity and fatal aortic rupture. Although surgical exclusion of an aneurysm can effectively prevent aortic rupture in large aneurysms, small aneurysms are generally completely asymptomatic and are very unlikely to rupture. Further, AAA can be easily diagnosed with noninvasive testing; thus, small aneurysms present an excellent opportunity for disease-modifying pharmacological intervention. Research over the past two decades has defined many of the mechanisms which result in aortic matrix degeneration in both human tissue and particularly within animal models. This has resulted in the identification of several potential targets for pharmacological intervention. Drugs directed at inhibition of the inflammatory process and matrix degrading enzymes have been successful in multiple animal models, and early evidence now suggests that disease modification with some of these agents may be successful in slowing AAA growth in humans as well. The future of AAA therapy, however, may belong to agents which can induce aneurysm regression and to delivery methods which specifically target affected arterial tissue.