Trichoderma strains have been widely used as part of strategies directed to attain sustainable agriculture considering that these fungi can reduce or substitute the utilization of agrochemicals. Species of this genus can prevent or eliminate fungal phytopathogens in agricultural crop systems by exerting plant colonization and fungal hyperparasitism. Extensive research has been developed on the biocontrol and biofertilizer activities of species of this genus in agricultural crops at field experimental scale, reporting biocontrol effectiveness from 35 to 100% for different crop-pathogen systems that include the following: Rhizoctonia (tomato), Fusarium (chickpea, green bean, tomato), Botrytis (cucumber), Sclerotinia (green bean, brinjal), and Pythium (green bean). Fungal inoculants most commonly employed at commercial scale are Trichoderma harzianum, T. viride, T. asperellum, and T. atroviride. In this review, a critical assessment was performed regarding the research carried out on the utilization of microbial species of the Trichoderma genus as a biological treatment in food crop production directed to plant-disease biocontrol, crop biofertilization, and abiotic stress modulation. In addition, the importance of the use of modern omics techniques on the systematics and taxonomy studies of crop-pathogen systems was addressed in order to build up a more comprehensive background to understand the functionality of the different species and strains in specific agricultural applications. Besides this, safety and production process considerations for inoculant product development are discussed as critical factors to foster the commercialization of Trichoderma inoculants and their exploitation in the agronomical sector. In conclusion, the prospects for Trichoderma-based inoculants as crop amendments are promising considering the multipurpose use of these fungal strains in agricultural systems and also the wide range of pathogenic biocontrol and their capability of the strains of this genus to establish symbiotic relationships with almost all kinds of plant crops, thus contributing to the development of sustainable agrosystems.