Cotton (Gossypium hirsutum) is the primary source of natural fiber for the textile industry worldwide. The US is a leading cotton producer and the largest exporter for the international cotton market, representing about US$7 billion annually. Reniform nematode (RN, Rotylenchulus reniformis) is a major pest for US cotton production. Annual seedcotton yield losses associated with RN are estimated at 1% representing approximately US$100 M loss in production. In the major cotton-producing states of Alabama, Louisiana, and Mississippi, RN has become the most important pest problem. Several approaches are required for RN management. Nematicides are effective in providing protection for cotton seedling development to enhance plant vigor and reduce yield losses, but the RN population will dramatically rebound during the cotton growing season. Rotation with non-host crops will reduce RN populations, but long rotational cycles are required to suppress the rapid recovery of the population. Growing resistant cultivars would be the most effective and sustainable strategy for long-term RN management. However, RN resistance was not found in the widely grown tetraploid upland cotton, thus hindering the rapid development of resistance cultivars. Several Sea Island cottons (G. barbadense) highly resistant to RN have been used to develop resistant upland cotton varieties. RN resistance was frequently observed in diploid Gossypium species. Our research focuses on introgression of RN resistance from diploid Gossypium species to upland cotton, understanding the genetics of resistance to enhance genetic diversity and developing genomic tools that can be applied for studying the genetics of resistance and for marker-assisted breeding.