The clinical use of lasers in surgery began in 1973 with applications of the carbon dioxide laser in otolaryngology, and since then the use of lasers has become commonplace in many medical and surgical specialties. Nonetheless, when biological tissue is subjected to laser radiation, the target cells can be vaporized, resulting in the aerosolization of their contents and the subsequent exposure of health care workers to laser-generated air contaminants (LGACs). The purpose of our analysis was to summarize and present all of the published literature pertaining to the laser-induced plume chemical and physical composition, health effects, and methods of control. The objective was to identify knowledge gaps within exposure science to set a research agenda for the protection of health care personnel exposed to LGACs. A literature search was performed using the PubMed database using a variety of search strategies and keyword combinations. To locate additional studies, we systematically searched the reference lists of all studies identified by our search, as well as key review papers. To date, researchers have identified roughly 150 chemical constituents of plume, as well as fine and ultrafine particulate matter, which has been shown to include viable cellular material, viruses, and bacteria. However, very few studies have attempted to characterize the effects of laser system type, power, and tissue treated, as it relates to LGAC exposure. Furthermore, current control strategies do not appear to be adequate in preventing occupational exposure to LGACs.