ABSTRACT Changing oxygen availability in lakes and reservoirs is a fundamental limnological challenge of our time, with massive consequences for freshwater ecosystem functioning and water quality. Cross-lake surveys, paleolimnological studies, and long-term monitoring records indicate that many lakes are exhibiting declines in both surface- and bottom-water oxygen availability due to climate and land use change, although a few lakes are exhibiting increases in oxygen. By analyzing time series of oxygen monitoring data from ∼400 lakes, I found that some lakes may be experiencing a decoupling of surface and bottom oxygen dynamics; variability in surface oxygen concentrations is decreasing in some lakes while variability in bottom oxygen concentrations is increasing. Changes in both oxygen concentrations and variability have many implications for lake functioning because oxygen concentrations control many ecosystem processes. Consequently, lake ecosystem provisioning and cultural services (e.g., drinking water, fisheries, recreation) will likely be impaired by declining oxygen, whereas the effects of changing oxygen on regulatory and supporting ecosystem services (e.g., nitrate removal through denitrification, carbon burial, sediment fluxes of phosphorus) may be more equivocal. These challenges motivate a research agenda focused on expanding the geographical range, temporal duration, and spatial extent of lake oxygen monitoring, as well as new approaches for studying and managing lakes (whole-ecosystem experiments, near-term oxygen forecasts). Looking ahead, advances in sensor technology, monitoring networks, data sharing, and forecasting, as well as the demonstrated success of environmental legislation in decreasing hypoxia, provide important opportunities for guiding restoration and science on lake oxygen.