An industry-funded, long-term, receiving water study was initiated in 1998/1999 to address questions about the potential effects of pulp and paper mill effluent discharges on US receiving waters. Although the study continues, the knowledge gained to date provides an opportunity to reflect on the study development process, its progress, and its outcomes. As a backdrop to a series of articles in this special issue describing study results, this article describes the process by which study information objectives were identified as well as the process by which the experimental design was developed. A review of past literature and research identified gaps in long-term population/community data about effluent effects and that, consequently, emerged as a primary information objective. The selected streams for study included 1) Codorus Creek (Pennsylvania, USA), 2) Leaf River (Mississippi, USA), 3) McKenzie River (Oregon, USA), and 4) Willamette River (Oregon) represent a blend of mill process types, coldwater and warmwater stream types, and a range of effluent concentrations. Measurements included numbers of periphyton, macroinvertebrate, and fish communities; the assessment of water and effluent quality; laboratory bioassays; and fish full–life-cycle assays. Information objectives included addressing natural variability and, consequently, the study included long-term temporal (>10 y) and watershed-scale spatial frameworks. Regional-scale ecological risk assessments were performed for each site that aided in placing each site in an ecological and regulatory context. An adaptive-management process is described that allowed for modifications over time as a result of lessons learned as the study progressed. Results from the initial 7 to 8 y of monitoring, as described in the series of articles in this special issue, provide a unique data set with respect to addressing point-source pulp and paper mill effluent discharge concerns and may serve as a template for others to use in developing monitoring or management programs to assess or address water quality conditions or concerns.