Rapid advances in gene-editing and stem-cell technology have expanded the range of possible future applications in human-animal chimera research. Most notably, recent developments may allow researchers to generate whole personalized human organs in pigs for the purpose of transplantation into human patients. Though human-animal chimera research in small animals, such as mice, is routine, human-animal chimeric techniques are now increasingly being applied to larger animals. Moreover, these chimeras include increasing amounts of human material, which is potentially present in more morally significant locations, such as the brain and the reproductive system. These developments raise important ethical questions about whether we should create such chimeras, and if so, how we should treat them. Answers to these ethical questions are needed to inform the development of policies regulating human-animal chimera research and its applications. Here, we provide a review of some of the most important or widespread ethical concerns.