Endophytic fungi are known to be abundant colonizers of the internal tissues of forest trees, but their ecological functions are still largely unknown. Recent studies indicate that endophytes may associate with tree's resistance and tolerance properties, and they are thus potential bio-agents that could be utilized in sustainable forest protection and management. To gain a better understanding of the endophytes' potential role in shaping forest health we need more evidence in the form of ecological studies of endophyte communities, in various tissues, across space, and time. The recent advances in molecular methods have given us new and effective tools to obtain such data. Studies of endophyte functions are further facilitated with the development of new high through-put screening methods for substrate use and competitive ability. Fungi are known as chemical factories of natural compounds with biological properties. Beside their potential as antagonists against pests and diseases, the tree-associated endophytic fungi therefore also appear as an emerging source of novel biomolecules for industrial or clinical applications outside forestry. This chapter presents some of the current methodological approaches that are likely to be valuable in studies on endophyte diversity in forest trees, and discusses the goals and impacts of the studies that aim at disentangling the beneficial potential of fungal endophytes in trees. A new concept, bioactive symbiosis, is suggested as a general framework for these studies.