Technical Abstract: Plant poisoning is often associated with a variety of livestock diseases and unexplained animal deaths. Although toxic plants commonly poison livestock and it is estimated to cost the livestock industry in the western United States more than $340 million every year, obtaining a definitive diagnosis is difficult and challenging. The purpose of this paper is to provide a framework to help veterinarians and diagnosticians make an accurate definitive diagnosis of plant poisoning. We provide suggestions for investigating and sampling field cases of suspected plant poisoning, where and how to analyze diagnostic samples, and for integrating information and recruiting appropriate expertise.