Diazaphenanthrene, indole, and several simple alkaloids are synthesized by the tall fescue plant. Peramine, ergot, and loline alkaloids are associated with the presence of the endophytic fungus N. coenophialum. All of the alkaloids found in tall fescue have biological activity in some bioassay. Accumulation of these alkaloids may be modified by management and the growing season. Results of research efforts are beginning to elucidate the genetics involved with perloline and the three groups of alkaloids associated with the fungal endophyte. Significant change in the accumulation of the alkaloids has been achieved by manipulation of the host grass or the endophyte. When different strains of the endophyte or a genetically modified strain are inserted into the host plant, the accumulation of alkaloids has been altered quantitatively and qualitatively. The presence of the endophyte provides agronomic benefits to the host, whereas the objective of endophyte change is to reduce animal toxicosis while maintaining the positive agronomic attributes. Insect resistance is a very positive characteristic, and the ability to move the gene clusters or enhance expression for loline alkaloid biosynthesis and accumulation into other endophyte strains and even into other agronomic plants is an intriguing possibility. Of more immediate interest is the need for definitive research to identify the toxin(s) and interactions involved in tall fescue toxicosis. There is much exciting and important research ahead.