Filamentous fungi are fungi with structures analogous to roots, playing an important role in nutrient and water absorption named hyphae, as well as extracellular digestion of organic compounds and mineralization of inorganic compounds. Some filamentous fungi have evolved interactions with plants and become endophytic. Endophytic fungi have a closer relationship with plants, improving their efficiency in obtaining energy and nutrients from plant cells. In return, they provide secondary metabolites such as phytohormones, proteins, enzymes, and other substances that play different roles in promoting plant growth, inducing resistance, and enhancing resistance to environmental stresses. Filamentous fungi also produce toxins capable of killing phytophagous insects responsible for significant economic losses in agriculture. This chapter aims to elucidate and discuss aspects related to the role of filamentous fungi as a source of diverse secondary metabolites and their use to face many challenges in agriculture. The use of filamentous fungi is an excellent alternative to face the major challenges of modern agriculture, which include reducing production costs, ensuring food security, and minimizing environmental impacts without compromising productivity. This chapter covers topics such as filamentous and endophytic fungi, biological control promoted by entomopathogenic fungi, the ability of fungi to enhance plant efficiency in soil exploration, and the promotion of plant resistance. All these effects are mediated by the synthesis of secondary metabolites produced by filamentous fungi and can be utilized to obtain various benefits in agricultural production, promoting sustainability and reducing the incidence of diseases and environmental degradation.