Diseases are increasingly threatening the conservation of wildlife species. Spillover of pathogens into humans and domestic animals may negatively impact public health and the economy, requiring increased proactive management actions. The North American Wildlife Management Model provides the philosophical basis for managing wildlife and underpins all management options. Diseases in wildlife populations may be managed by manipulation of the environment, manipulation of the host, manipulation of the agent, and modification of human behavior. Important considerations include setting management goals, and metrics to assess success. Future strategies include using systems and One Health approaches to develop interventions that optimize outcomes for humans, animals, and the environment.