The ATP-binding cassette (ABC) transporter superfamily contains membrane pr
oteins that translocate a variety of substrates across extra- and intra-cel
lular membranes. Genetic variation in these genes is the cause of or contri
butor to a wide variety of human disorders with Mendelian and complex inher
itance, including cystic Fibrosis, neurological disease, retinal degenerati
on, cholesterol and bile transport defects, anemia, and drug response. Cons
ervation of the ATP-binding domains of these genes has allowed the identifi
cation of new members of the superfamily based on nucleotide and protein se
quence homology. Phylogenetic analysis is used to divide all 48 known ABC t
ransporters into seven distinct subfamilies of proteins. For each gene, the
precise map location on human chromosomes, expression data, and localizati
on within the superfamily has been determined. These data allow predictions
to be made as to potential functions or disease phenotypes associated with
each protein. In this paper, we review the current state of knowledge on a
ll human ABC genes in inherited disease and drug resistance. In addition, t
he availability of the complete Drosophila genome sequence allows the compa
rison of the known human ABC genes with those in the fly genome. The combin
ed data enable an evolutionary analysis of the superfamily. Complete charac
terization of all ABC from the human genome and from model organisms will l
ead to important insights into the physiology and the molecular basis of ma
ny human disorders.