The pathogenesis of tall fescue toxicosis in animals is due in part to effects of alkaloids, among which ergovaline is prominent, on the cardiovascular system. The effects include thickened blood vessels, increased vascular tone, hypercoagulability and sludging of blood, and, depending on severity, ischemia and gangrenous necrosis of tissues. The ischemic response of blood vessels in the skin and lungs contributes to heat stress problems and also likely influences reproductive performance and nutrient flux in the gastrointestinal system. The well-known effect of alkaloids on reducing feed intake may have an associated effect on important nutrient factors. In support of this supposition, a trend has been demonstrated for increased tryptophan levels to occur in the blood of cattle that had grazed E+ tall fescue. This increase may have an impact on serotonin levels in the hypothalamus and subsequently may affect feeding behavior. Similarly, a suppressive effect of E+ tall fescue intake on serum arginine levels has been demonstrated. The decrease in serum arginine has been linked to decreased nitric oxide availability that may ultimately enhance vasoconstrictive and hypercoagulability effects. All these biological effects have the potential to affect efficiency of production. This lost efficiency results in increased production costs, which ultimately diminish sustainability of forage-animal production. This problem likely will be solved by a variety of treatments and management protocols aimed at improving animal tolerance or limiting exposure to E+ tall fescue. Both approaches require more fundamental biological information concerning the exact causative agents and the mechanisms involved.