Technical Abstract: Plantings of tall fescue were numerous in Kentucky during the 1940s and 1950s after the cultivar, ‘Kentucky 31’, was released. Its hardiness and adaptability resulted in the grass spreading over much of the middle and upper southeastern USA. Cases of severe lameness and sloughing of hoofs, tails, and ear tips during cold weather, and poor weight gain and thriftiness during warm weather conditions were soon reported for cattle grazing tall fescue pastures. Reductions in calving rates and milk production were also of concern. Horse producers identified serious issues with grazing pregnant mares (prolonged gestation, retained placentas, stillborns, and poor milk production) on tall fescue. It was determined that ergot alkaloids produced by a fungal endophyte that infects the grass were eventually determined to be the cause of the fescue toxicosis syndrome. Complexities of the biological processes and the chemistry of alkaloids have made it difficult to understand how ergot alkaloids affect animal tissues. However, researchers now have the tools needed to improve our understanding of the causes of toxicosis. The paper will discuss our understanding of the mechanisms by which ergot alkaloids affect 1) vascular blood flow, 2) hair shedding and growth during the summer, and 3) circulating concentrations of prolactin. Although, considerable progress has been made over the last 10 years, more research is needed to fully understand the toxicosis syndrome.