Since first hypothesizing the existence of nanobubbles (NBs) in 1994, the empirical study of NB properties and commercialization of NB generators have rapidly evolved. NBs are stable spherical packages of gas within liquid and are operationally defined as having diameters less than 1000 nm, though they are typically in the range of 100 nm in one dimension. While theories still lack the ability to explain empirical evidence for formation of stable NBs in water, numerous NB applications have emerged in different fields, including water and wastewater purification where NBs offer the potential to replace or improve efficiency of current treatment processes. The United Nations identifies access to safe drinking water as a human right, and municipal and industrial wastewaters require purification before they enter water bodies. These protections require treatment technologies to remove naturally occurring (e.g., arsenic, chromium, fluoride, manganese, radionuclides, salts, selenium, natural organic matter, algal toxins), or anthropogenic (e.g., nitrate, phosphate, solvents, fuel additives, pharmaceuticals) chemicals and particles (e.g., virus, bacteria, oocysts, clays) that cause toxicity or aesthetic problems to make rivers, lakes, seawater, groundwater, or wastewater suitable for beneficial use or reuse in complex and evolving urban and rural water systems. NBs raise opportunities to improve current or enable new technologies for producing fewer byproducts and achieving safer water. This account explores the potential to exploit the unique properties of NBs for improving water treatment by answering key questions and proposing research opportunities regarding (1) observational versus theoretical existence of NBs, (2) ability of NBs to improve gas transfer into water or influence gas trapped on particle surfaces, (3) ability to produce quasi-stable reactive oxygen species (ROS) on the surface of NBs to oxidize pollutants and pathogens in water, (4) ability to improve particle aggregation through intraparticle NB bridging, and (5) ability to mitigate fouling on surfaces. We conclude with key insights and knowledge gaps requiring research to advance the use of NBs for water purification. Among the highest priorities is to develop techniques that measure NB size and surface properties in complex drinking and wastewater chemistries, which contain salts, organics, and a wide variety of inorganic and organic colloids. In the authors' opinion, ROS production by NB may hold the greatest promise for usage in water treatment because it allows movement away from chemical-based oxidants (chlorine, ozone) that are costly, dangerous to handle, and produce harmful byproducts while helping achieve important treatment goals (e.g., destruction of organic pollutants, pathogens, biofilms). Because of the low chemical requirements to form NBs, NB technologies could be distributed throughout rapidly changing and increasingly decentralized water treatment systems in both developed and developing countries.