Objective This review describes ongoing efforts to develop a medical therapy to limit abdominal aortic aneurysm (AAA) growth. Methods Data from animal model studies, human investigations, and clinical trials are described. Results Studies in rodent models and human samples have suggested a number of potential targets for slowing or halting AAA growth. A number of clinical trials are now examining the value of medications targeting some of the pathways identified. These trials have a number of challenges, including identifying medications safe to use in older patients with multiple comorbidities, developing accurate outcome assessments, and minimizing the dropout of patients during the trials. Three recent trials have reported no benefit of the antibiotic doxycycline, a mast cell inhibitor, an angiotensin-converting enzyme inhibitor, or a calcium channel blocker in limiting AAA growth. A number of other trials examining angiotensin receptor blockers, cyclosporine, and an antiplatelet agent are currently underway. Conclusions Further refinement of drug discovery pathways and testing paradigms are likely needed to develop effective nonsurgical therapies for AAA.