Microbial products have a long history of safe use and most of the microbial agents are compatible with other methods of pest control. A number of microbial biopesticides have been registered for fi eld application on various vegetables, fruits, and other crops of agricultural, horticultural, and forest importance. During sporulation phase, Bacillus thuringiensis accumulates certain insecticidal crystal proteins which are pathogenic to a number of insect orders. Thousands of toxicogenic strains of B. thuringiensis exist and each strain produces its own unique well-known insecticidal crystal protein. B. thuringiensis is biodegradable and safe to nontarget organisms as the conditions required for complex steps in the mode of action do not exist in mammals or most of invertebrates. Development of agricultural crop varieties that contain B. thuringiensis proteins provides a safe alternative to the use of chemical insecticides. Tobacco and tomato were the fi rst transgenic plants encoding for B. thuringiensis insecticidal crystal protein. The development of resistance to B. thuringiensis toxins is, however, particularly unfortunate. Thousands of B. thuringiensis isolates are available around the world, and fortunately almost all the major insect pests are susceptible to these strains. Moreover synthetic insecticides in combination with biopesticides are economic, 278 effective, and eco-friendly. The aim of this chapter is to focus on the potentiality of B. thuringiensis in the management of pernicious lepidopteran pests and their mode of their interactions to develop the cost-effective medium for the formulation of biopesticides.