Control of insect pests in agriculture and of insect vectors of important human diseases is mainly achieved using chemical insecticides. However, use of these chemical insecticides has led to several problems, including environmental pollution and increase in human health problems, such as cancer and several immune system disorders. Although microbial insecticides have been proposed as substitutes for chemicals, their use is limited since most microbes show a narrow spectrum of activity. Moreover, they have low environmental persistence and they require precise application practices, since many of these microbes are specific to young insect larval stages. Isolation and characterization of new insecticidal activities is the target of many pest control programs. Bacillus thuringiensis Berliner (130 is a gram positive spore forming bacteria. It forms a spore in an adverse condition. Bt produces protein crystals during sporulation. The protein crystals are consisted of two multigenic families, Cry and Cyt. Cry proteins are toxic to different insect orders. They are toxic to Lepidoptera, Coleoptera, Hymenoptera, Diptera and to nematodes. However, Cyt proteins are toxic mostly against Diptera. Prolonged and continuous use of Bt toxin has led to the development of resistance in three species of lepidopteran insects. Moreover, these crystal proteins have not been able to provide protection against all the groups of the agronomical harmful pests. In view of this situation, the recently reported vegetative insecticidal proteins (VIPs), a group of vegetative insecticidal proteins, produced during vegetative stage of bacterial growth from Bt seems to provide the possible solution. In this review, a great team of experts gathered to bring together all recent studies regarding both fundamental and more applied research aspects related to Bt to give a tour of the whole story of Bt since its discovery and comprehensively update the entire subject. Finally, the future challenges and prospects of Bt.