The Segregation Distorter (SD) system of Drosophila melanogaster is one the best‐characterized meiotic drive complexes known. SD gains an unfair transmission advantage through heterozygous SD/SD+ males by incapacitating SD+‐bearing spermatids so that virtually all progeny inherit SD. Segregation distorter (Sd), the primary distorting locus in the SD complex, is a truncated duplication of the RanGAP gene, a major regulator of the small GTPase Ran, which has several functions including the maintenance of the nucleocytoplasmic RanGTP concentration gradient that mediates nuclear transport. (...) The truncated Sd‐RanGAP protein is enzymatically active but mislocalizes to the nucleus where it somehow causes distortion. Here I present data consistent with the idea that wild‐type RanGAP, and possibly other loci able to influence the RanGTP gradient, has been caught up in an ancient genetic conflict that predates the SD complex. The legacy of this conflict could include the unexpectedly rapid evolution of nuclear transport‐related proteins, the accumulation of chromosomal inversions, the recruitment of gene duplications, and the turnover of repetitive sequences in the centric heterochromatin. BioEssays 29:386–391, 2007. © 2007 Wiley Periodicals, Inc. (shrink)