In this article the authors defined harvest-based monitoring as the long-term collection of data or samples from a subsistence harvest in order to reveal, document, and track changes in biophysical resources. The objective of the article was to describe five practical steps that have guided us over the past two decades during the delivery of harvest-based monitoring studies in the Inuvialuit Settlement Region (ISR). Studies have usually been designed to detect (but not necessarily explain) change, to involve local harvesters, and to incorporate indigenous and science-based knowledge. The five steps are to (1) formulate a scientific research or long-term monitoring question that can reasonably be answered by analyzing data from harvests or harvested specimens, (2) design the program according to scientific and indigenous protocols, (3) determine respective partner roles for delivery of the field program, (4) conduct the field work, and (5) analyze data and communicate results. At all steps, it is important to ensure that science and indigenous knowledge partners respect and trust each other’s skills, knowledge, and abilities; that regular communication is fostered; and that provisions are in place to monitor progress. The credible blending of indigenous and scientific views and skills improves the likelihood of ultimately understanding the resource, its habitats, and its inherent ecological relationships.