Health research in the context of an environmental disaster with implications for public health raises challenging ethical issues. This article explores ethical issues that arose in the Gulf Long-term Follow-up Study (GuLF STUDY) and provides guidance for future research. Ethical issues encountered by GuLF STUDY investigators included a) minimizing risks and promoting benefits to participants, b) obtaining valid informed consent, c) providing financial compensation to participants, d) working with vulnerable participants, e) protecting participant confidentiality, f) addressing conflicts of interest, g) dealing with legal implications of research, and h) obtaining expeditious review from the institutional review board (IRB), community groups, and other committees. To ensure that ethical issues are handled properly, it is important for investigators to work closely with IRBs during the development and implementation of research and to consult with groups representing the community. Researchers should consider developing protocols, consent forms, survey instruments, and other documents prior to the advent of a public health emergency to allow for adequate and timely review by constituents. When an emergency arises, these materials can be quickly modified to take into account unique circumstances and implementation details. © 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved.