The spread of medusahead across the western United States has severe implications for a wide range of ecosystem services. Medusahead invasion reduces biodiversity, wildlife habitat and forage production, and often leads to increased fire frequency and restoration costs. Medusahead is problematic in the Intermountain West and California Annual Grasslands. The last review of medusahead ecology and management was completed 20 years ago. Since the last review, there have been scientific advances in medusahead management suggesting a significant need to develop an up-to-date synthesis. Medusahead continues to pose a serious threat to rangeland ecosystems. In this synthesis, we present new information regarding the ecology of medusahead, suggest a framework for managing medusahead based on invasion level, and identify research needs to further improve management of this invasive annual grass. Success of different management practices varies between the Intermountain West and California Annual Grasslands, signifying that the best management practices are those specifically tailored with consideration of climate, soil, plant community characteristics, and management objectives. Prevention and control treatments that are useful in the Intermountain West may not be practical or effective in the California Annual Grasslands and vice-versa.