The types of changes in physical appearance and behavior that occur in elderly people similarly develop in elderly animals. Signs and symptoms that might cause concern in younger people or mice may be normal in their elderly but generally healthy counterparts. Although numerous scoring methods have been developed to assess rodent health, these systems were often designed for young adults used in specific types of research, such as cancer or neurologic studies, and therefore may be suboptimal for assessing aging rodents. Approaches known as frailty assessments provide a global evaluation of the health of aged mice, rats, and people, and mouse frailty scores correlate well with the likelihood of death. Complementing frailty assessment, prediction of imminent death in aged mice can often be accomplished by focusing on 2 objective parameters-body weight and temperature. Before they die, many (but not all) mice develop marked reductions in body weight and temperature, thus providing signs that close monitoring, intervention, or preemptive euthanasia may be necessary. Timely preemptive euthanasia allows antemortem collection of data and samples that would be lost if spontaneous death occurred; preemptive euthanasia also limits terminal suffering. These approaches to monitoring declining health and predicting death in elderly research mice can aid in establishing and implementing timely interventions that both benefit the research and reduce antemortem suffering.