Liquid breathing has been proposed as a means of improving gas exchange in infants with acute respiratory failure since the 1970s. In addition, there are potential clinical applications of perfluorochemical (PFC) liquids that span many specialties in medicine. The ability to lower surface tension directed the initial clinical focus on neonatal therapy in the treatment of premature lung disease. The first clinical trial of PFC ventilation was performed in neonates in 1989. Additional trials using LiquiVent (Alliance Pharmaceutical San Diego, CA), a medical grade PFC liquid, were initiated in 1993 in infants, children, and adults. These studies have concluded that liquid ventilation appeared to be safe, improve lung function, and recruit lung volume in patients from these populations. The results of such trials are encouraging, but randomized trials have yet to be completed. We await these pivotal trials, which will probably be completed in adult patients first, before this promising technique can be clinically available.