Mosquito-borne diseases such as malaria, dengue, chikungunya, and filariasis continue to pose a serious public health challenge in India. Vector control remains central to managing these diseases, with insecticides forming the backbone of control programs. However, the effectiveness of these chemicals has declined as mosquito populations have developed resistance, while drug resistance has also emerged in pathogens. Resistance in mosquitoes is driven by multiple mechanisms, including enhanced detoxification processes and mutations that reduce insecticide sensitivity. This review traces the history of insecticide use in India, focusing on the five major classes - organochlorines, organophosphates, pyrethroids, carbamates, and neonicotinoids. Prolonged use has led to widespread resistance in key species such as Anopheles culicifacies, An. stephensi, Culex quinquefasciatus, and Aedes aegypti. The review highlights target-site mutations (such as kdr L1014F/S, F1534C), metabolic resistance (CYP450s, GSTs, esterases), behavioral changes, and cuticular thickening. Resistance patterns vary across regions and often involve multiple classes of insecticides. Recent molecular findings offer important insights for surveillance and provide direction for integrated and sustainable resistance management strategies in India.