Angioedema, characterized by swelling of the lips, face, and tongue, occurs in anywhere from 0.1% to 6% of angiotensin-converting enzyme (ACE) inhibitor users. The incidence is more common in black Americans than in white Americans, in women than in men, and in smokers than in nonsmokers. The remitting and relapsing nature of ACE inhibitor-associated angioedema can confound clinical recognition of the adverse event but also provides clues to its causes. Defective degradation of vasoactive peptide substrates of ACE, such as bradykinin or substance P, may contribute via non-ACE pathways to the pathogenesis of ACE inhibitor-associated angioedema.