The 2016 vote to leave the European Union (EU) shocked British scientists. The European Union enjoys strong support from researchers across United Kingdom academia and industry, with 17% of all U.K. university science contracts now funded by the European Union, accounting for 73% of the growth in U.K. university science budgets in recent years ( 1 ). These EU funds support high-value multinational collaborations. Free movement of researchers within the European Union ensures flow of talent to where it is most needed and helps early career researchers acquire scarce skills. U.K. scientists have enjoyed access to EU research infrastructure and strong influence on shared regulatory systems. Facing potential exclusion from a global science powerhouse that it has done so much to shape, how should the United Kingdom disentangle itself from this 40-year old collaboration? We propose an eight-point plan to limit the immediate damage and to put U.K. science on the front foot in the wake of the Brexit vote.