Solute carriers (SLCs) is the largest group of transporters, embracing transporters for inorganic ions, amino acids, neurotransmitters, sugars, purines and fatty acids among other substrates. We mined the finished assembly of the human genome using Hidden Markov Models (HMMs) obtaining a total of 384 unique SLC sequences. Detailed clustering and phylogenetic analysis of the entire SLC family showed that 15 of the families place into four large phylogenetic clusters with the largest containing eight SLC families, suggesting that many of the distinct families of SLCs have a common evolutionary origin. This study represents the first overall genomic roadmap of the SLCs providing large sequence sets and clarifies the phylogenetic relationships among the families of the second largest group of membrane proteins.