Bisphosphonates suppress bone turnover by disrupting osteoclast signal transduction, maturation, and longevity. In some patients, it has been hypothesized that suppressed turnover can impair oral wound healing, leading to a distressing, osteopetrosis-like jaw necrosis called bisphosphonate-related osteonecrosis of the jaws (BRONJ). Hyperbaric oxygen (HBO), as an adjunct to surgery and antibiotics, might have utility in the treatment of BRONJ because it produces reactive oxygen and nitrogen species that positively modulate the redox-sensitive intracellular signaling molecules involved in bone turnover. The efficacy of HBO in the treatment of BRONJ is currently under investigation in randomized controlled trials at Duke University and the University of Minnesota, and the early results have been encouraging. This report discusses osteoclast biology, how HBO has the potential to augment bone turnover by way of the signaling effects on osteoclasts, the available clinical data on HBO in the treatment of BRONJ, the ongoing randomized controlled trials of HBO, and the study-associated efforts to find biomarkers to characterize an individual's risk of developing this disease.