2007, Springer-Verlag Berlin Heidelberg. Cotton is the most important natural fiber that has been used for over seven millennia to meet the clothing requirement of mankind. In addition to the fiber, the plant also provides seed, linters, and hull that are used for food, feed, and several other diverse applications. The cotton plant is also susceptible to a large number of pests and pathogens. Traditionally, its cultivation has heavily relied on the use of toxic pesticides. Thus, compared with many other crops, it offers a much larger number of targets that can be modified through the use of modern biotechnological tools. Genetically engineered cotton, offering only insect- and herbicide-resistance traits, has gained rapid and wide acceptance in many cotton-growing countries around the globe. However, this plant also offers many challenges in terms of genetic modification, largely due to its recalcitrance to regeneration in tissue culture. This chapter provides a comprehensive account of the methods and tools needed to transform cotton, important traits introduced into this plant, and the possibilities offered for crop improvement through recent advances in genetic modification technologies.