Managing wildlife populations on a landscape is not a new concept to the field of wildlife management. However, a variety of barriers exist to effectively manage wildlife species at landscape scales. For example, competing management objectives for the same population can occur in parts of two adjoining states and 3-4 agencies within a single state may be charged with managing the habitat on which that population depends at varying spatial scales. Moreover, most state and federal agencies have different mandates and implement management actions out of offices that have static administrative or jurisdictional boundaries. Hence, implementing management actions across relatively large spatial extents can be difficult because one manager or one agency field office may have little or no input on the management of habitats or populations for which they do not have administrative responsibility. In contrast, landscape ecologists often focus on actions that ignore those same logistical hurdles. Landscape ecologists and wildlife managers should be aware of such barriers and incorporate these unique challenges and constraints into their research questions, proposed management actions, and policies. Our goal is to identify challenges, constraints, and opportunities to managing wildlife populations at a landscape scale and describe how resource agencies and landscape ecologists can work collaboratively to overcome challenges and constraints. We also explore the potential management challenges created by continuing to manage wildlife populations and habitats based on local-scale approaches to management and decision making. Finally, we provide a case study using the greater sage-grouse as an example of challenges and constraints to managing a species at a landscape scale.