Unfamiliar approaches to training, legal and regulatory complications, and differences in funding and administration pose challenges for collaboration that are then compounded by the need to satisfy the requirements of different research systems. To help today’s international researchers create the best possible partnerships, chapters by funding officers, diplomats, attorneys, publishers, regulators, graduate students and postdocs, industry researchers, administrators, and scholars of responsible research address the following key trouble spots: will provide valuable insights to researchers who are collaborating or who intend to collaborate, as well as to administrators, funders, regulators, editors, and policy-makers involved in cross-national research.