Obtaining spatially explicit, cost-effective, and management-relevant data on invasive plant distributions across large natural areas presents considerable challenges. This is especially true when multiple monitoring objectives exist, because the utility of different monitoring methodologies varies with scale, logistical considerations, and information needs. The Florida Everglades is a vast wetland landscape with widespread invasive plant infestations and multiple management jurisdictions. A multi-agency team Working Group conducted a workshop in 2013 to explore opportunities to enhance the performance of a regional weed control program. Among the most important developments occurring at this meeting was the recognition that relevant management questions are scale-dependent. This led the team to define multiple monitoring objectives. Essential for conveying the success of the weed management program is quantifying large-scale patterns of change, as are quantifying finescale patterns informing control activities, defining mechanisms of spread, recognizing accelerating rates of spread, and detecting patterns of occupancy immediately before management intervention. The group's deliberation resulted in the emergence of a multiscale monitoring program utilizing several distinct monitoring protocols, including systematic landscape-level reconnaissance, a sample-based spatially stratified monitoring system, detailed inventories in planned treatment areas, and a set of methods focused solely on early detection and rapid response. Here we provide an overview of the Everglades multiscale invasive plant monitoring program, highlight benefits and challenges of each program component, and discuss how this program has improved regional invasive plant management.