After nearly 2 centuries of being negatively impacted, primarily by introduced mainland vertebrates, the unique flora and vegetation of the Islands of the Californias archipelago have been severely degraded. The botanical conservation challenges that lie ahead include the near extinction or extirpation of rare, endemic, and even common plant taxa; invasion of nonnative plants; near loss of unique island vegetation communities; and the degradation of a host of sites. These challenges are too large for any one entity to remedy alone. Many of the botanical resources impacted are found on multiple islands and cross political boundaries. The Islands of the Californias managers and their mainland partners have formalized a binational collaboration, the Islas de las Californias, Colaboración Botánica, or Islands of the Californias Botanical Collaborative (ICBC), to address these challenges more effectively and efficiently and thus achieve greater conservation success. The ICBC has identified and prioritized challenges in botanical resource management, taken actions to recover plant populations at risk and prevent future extinctions, developed tools to evaluate plant reintroductions, implemented quarterly meetings to share professional experiences, begun to develop tools for information and data sharing, and leveraged multi-island efforts for botanical resources funding. Herein we present our rationale for this collaborative and detail our progress toward creating archipelago-wide groups comprising the Invasive Plant Management Network, Plant Extinction Prevention Program, Native Plant Restoration Program, Integrated Biodiversity Information System, and Work Share Program.