Prevalence of alternate host and high recombination ability of various virulent strains makes it a daunted task to overcome the CLCuD, a barrier to serve high yield and improved fibre quality for cotton worldwide. Prevalence of Virulent viral strains, availability of alternate host plants and high recombinant strains are the major setback in controlling this disease. This tenacious Cotton leaf curl Virus (CLCuV), is spread by the whitefly Bemisia tabaci and belongs to family begomoviruses called Geminiviridae. Different ways to control this disease had been explored such as development of resistant varieties, vector control and eradication of weeds harbouring CLCuD. With the advent of high throughput technologies in biotechnology field, it had become possible to actually sequence the complex Gossypium species like G. arbroeum and G. raimondii. However, there is very scanty information available about the molecular transmission of inheritance of resistance in various cotton varieties. Further, the molecular data may offer insights into the virus genome's complexity, identity of its sequence, genetic variability, and recombination analysis for the development of virus-based illness management strategies. In this review, detailed discussion has been presented on the genetic basis of CLCuD inheritance, development of resistant cotton varieties, and role of genetic engineering in combating CLCuD through transgenic approaches.