Saline and indocyanine green dye were the first agents noted to produce a contrast effect when injected peripherally during M-mode echocardiographic imaging, although it was subsequently found that almost any type of injected solution would have this effect. These first-generation contrast agents were limited to opacification of right heart structures, and they prompted subsequent development of agents that traverse pulmonary circulation. Although opacification limited to right heart structures is considered a limitation of these first-generation agents, this is an advantage when attempting to identify the presence of right-to-left shunt. First-generation air contrast is considered the gold standard for identification of patent foramen ovale (PFO). However, PFO investigators have used varying criteria to define abnormal contrast studies. There are also multiple mechanisms by which saline contrast studies may produce both false-positive and false-negative results for presence of PFO. There is mounting experimental evidence that PFO is associated with cerebral ischemia and migraine headache, with a resulting evolution of devices for percutaneous closure of these shunts. Echocardiographic physicians must be aware of potential pitfalls of the air contrast technique to avoid exposing patients to unnecessary risk of closure devices, and missing the potential benefit of shunt closure in appropriately selected patients.