With the growth of animal-assisted interventions, the number of animals designated to work as therapy animals continues to increase. These animals participate in this work in varying capacities during life, but there will be a point in time when the animal can no longer engage in these activities. The concept of retirement, or withdrawing the animal from its working life, is an important phase of life that every therapy animal will inevitably face. Retirement is typically regarded as a well-deserved reward earned after a lifetime of work, but this termination of an animal’s career has potential positive and negative implications for animal, handler, and human participants in these interventions. The question of precisely when and how to appropriately retire an animal is usually answered at the discretion of the handler; however, the validity of this question remains largely unanswered without scientific evidence. The purpose of this review is to describe the implications of therapy animal retirement for the handler, participant, and animal and to discuss the challenges in determining when to retire a therapy animal.