The recent arrests of Chinese nationals for alleged economic espionage are raising eyebrows across American industries, who are rightfully asking how they can protect themselves from becoming the next foreign target. U.S. universities have been key figures in these headlines. The risk of economic espionage is a serious one for higher education because universities are often in the position of balancing open and collaborative research goals with tight government restrictions on data use. But for those universities contracting with the U.S. government, compliance with its information security regulations is often not optional. Here, we explore how recent and expected rules regarding both classified and unclassified information could make universities’ work in this space a complicated endeavor.