The advent of genetic engineering has revolutionized agriculture remarkably with the development of superior insect-resistant crop varieties harboring resistance against insect pests. Bacillus thuringiensis (Bt) has been used as a main source for insect-resistant genes. In addition to Bt endotoxins, various plant lectins and other non-Bt genes from different sources have also been introduced in crop plants of economic importance. The insect-resistant crops have made a huge economic impact worldwide since their commercial release. The cultivation of insect-resistant cultivars has resulted both in increased crop productivity and in decreased environmental pollution. Although insect-resistant crops have been allowed to be commercialized following proper biosafety guidelines and procedures, still these crops face many challenges in order to be fully adopted and accepted. The degradation kinetics of Bt proteins, horizontal and vertical gene flow, effects on nontarget insects or organisms, antibiotic resistance, and some other unintended effects have been noted and discussed. Although no concrete evidence regarding any significant hazard of genetically engineered crops has been presented so far, the debate still remains intense. Impartial and professionally competent regulatory mechanisms for the evaluation of insect-resistant and other transgenic crops must be fully functionalized. The first part of this review focuses the development of different insect-resistant crops and various strategies adapted to delay resistance development in insect pests, while the second part addresses the challenges and future prospects of insect-resistant crops.