The growing demand for food due to the expansion of world population necessitates development of practices that will enable high-yield, disease-free agriculture, with minimal use of chemical pesticides. Biocontrol-associated microorganisms can inhibit disease by either directly antagonizing phytopathogens or by stimulating a state of induced resistance in plants. Certain agronomic practices such as amendment of compost and biochar to soil curb plant disease by stimulating abundance and activity of indigenous soil and root-associated biocontrol agents (BCAs) resulting in so called “suppressive soils.” Over the past half century, a multitude of attempts have been made to implement both BCAs and agronomic agricultural practices as plant protection strategies. Nonetheless, the use of these strategies in large-scale commercial agriculture is still very limited due to restricted efficacy and consistency. The following chapter focuses on well-documented BCAs and their modes of action, delineates microbial-associated biocontrol-inducing agronomic practices, and discusses future directions required for applying biocontrol in high-yield sustainable agriculture.