Grasses are noted for an absence of toxic secondary metabolites. However, some grass-associated fungi are known for their production of numerous secondary compounds, which serve important functions such as plant competition and resistance to biotic and abiotic stresses. Cohabitation of certain fungi with grasses has developed into specific mutualistic associations. The fungi of concern belong to a relatively small group of species within the Clavicipitaceae. This group of fungi shares a common feature in being endophytically associated with grasses as obligate biotrophic symbionts. Specific attention is given to two related genera Epichloë and their anamorphic Neotyphodium relatives. The association of these fungi with grasses results in the accumulation of several classes of fungal metabolites that serve as relief mechanisms to biotic and abiotic stresses. These include drought tolerance, resistance to vertebrate and invertebrate pests, resistance to fungal diseases, and tolerance to poor soil conditions. Resistance to multiple stresses can occur simultaneously within the same symbiotum. The resulting resistance to multiple stresses, along with inter- and intra-specific competitive advantage suggests the potential for utilizing novel fungal endophytes new host combinations for stress resistance in naturally infected grasses as well as for resistance to specific agronomic and ecological conditions and soil remediation.