Native salmonid populations in the inland West are often restricted to small isolated habitats at risk from invasion by nonnative salmonids. However, further isolating these populations using barriers to prevent invasions can increase their extinction risk. This monograph reviews the state of knowledge about this tradeoff between invasion and isolation. We present a conceptual framework to guide analysis, focusing on four main questions concerning conservation value, vulnerability to invasion, persistence given isolation, and priorities when conserving multiple populations. Two examples illustrate use of the framework, and a final section discusses opportunities for making strategic decisions when faced with the invasion-isolation tradeoff.