Technical Abstract: Cotton fiber is an economically important seed trichome and the world's leading natural fiber used in the manufacture of textiles. As a step towards elucidating the genomic organization and distribution of gene networks responsible for cotton fiber development, we investigated the distribution of fiber genes in the cotton genome. Results revealed the presence of gene-rich islands for fiber genes with a biased distribution in the tetraploid cotton (Gossypium hirsutum L.) genome that was also linked to discrete fiber developmental stages based on expression profiles. There were three fiber gene-rich islands associated with fiber initiation on chromosome 5, three islands for the early to middle elongation stage on chromosome 10, three islands for middle to late elongation stage on chromosome 14, and one island on chromosome 15 for secondary cell wall deposition (SCWD) for a total of ten fiber gene-rich islands. Clustering of functionally related gene clusters in the cotton genome displaying similar transcriptional regulation indicates an organizational hierarchy with significant implications for the genetic enhancement of particular fiber quality traits. The relationship between gene-island distribution and functional expression profiling suggests for the first time the existence of functional coupling gene clusters in the cotton genome.