Lichens are often regarded in nature as the most successful symbiosis between a fungus and a photosynthetic partner. Interestingly, endolichenic fungi, another lichen-associated microorganisms, has been recently discovered living within the lichen thalli. The production of metabolites previously identified from plants by its associated fungi led natural product researchers to tap endophytic microorganisms such endolichenic fungi for drug discovery. In this 3-year Project ELFHA, endolichenic fungi will be isolated from four native species of Usnea collected from eight sampling localities in the Philippines. The host lichen Usnea and its associated endolichenic fungi will be identified by conventional morphological and modern molecular (DNA barcoding) methods which could lead to taxonomic revision of the host lichens and/or discovery of new species of endolichenic fungi. The endolichenic fungi will then be screened for their inhibitory activities against plant pathogenic fungi (for agricultural application) and the ESKAPE bacterial pathogens (for health application). To hasten the discovery process, three promising ELF will be subjected to OSMAC approach for the production of secondary metabolites via solid-state fermentation of indigenous substrata and to metabolomic profiling for early detection of novel compounds. Metabolomic analysis facilitates rapid identification of extracts with possible novel metabolites without the need for compound purification, isolation, and structure elucidation. Then, the crude culture extract from a “talented” ELF, i.e., a fungal isolate with high metabolic diversity, strong bioactivity, and taxonomic novelty, will be fractionated, and tested against an antibiotic-resistant bacterium (methicillin-resistant Staphylococcus aureus) and fungicide-resistant fungus (azole-resistant Fusarium graminearum). Project ELFHA generally aims to discover novel endolichenic fungi with novel bioactive metabolites.