Horticultural crops are vulnerable to diverse microbial infections, which have a detrimental impact on their growth, fruit quality, and productivity. Currently, chemical pesticides are widely employed to manage diseases in horticultural crops, but they have negative effects on the environment, human health, soil physiochemical properties, and biodiversity. Additionally, the use of pesticides has facilitated the development and spread of resistant pathovars, which have emerged as a serious concern in contemporary agriculture. Nonetheless, the adverse consequences of chemical pesticides on the environment and public health have worried scientists greatly in recent years, which has led to a switch to the use of biocontrol agents such as bacteria, fungi, and insects to control plant pathogens. Biocontrol agents (BCAs) form an integral part of organic farming, which is regarded as the future of sustainable agriculture. Hence, harnessing the potential of BCAs is an important viable strategy to control microbial disease in horticultural crops in a way that is also ecofriendly and can improve the soil health. Here, we discuss the role of the biological control of microbial diseases in crops. We also discuss different microbial-based BCAs such as fungal, bacterial, and viral and their role in disease management. Next, we discuss the factors that affect the performance of the BCAs under field conditions. This review also highlights the genetic engineering of BCAs to enhance their biocontrol efficiency and other growth traits. Finally, we highlight the challenges and opportunities of biocontrol-based disease management in horticulture crops and future research directions to boost their efficacy and applications.