Charles Darwin remarked that “males, with their superior strength, pugnacity, armaments, unwieldly passion and love songs, are almost always the more active and most often, the initiators of sexual interactions”.1 Here, we propose that such male sex drive directly impacts the genome by leading to its progressive masculinization—genes that possess sex-specific effects on male fitness accumulate to a much greater extent and are generally more diverged.2,3 The larger proportion of male versus female fitness modifiers in combination with stronger sexual selection may generate evolutionary signatures such as a greater sensitivity to male sterility4 and a paucity of X-linked male-specific genes.5–8 Male sex-drive theory complements the female-choice theory of sexual selection and allows for the genetic variation of costly sexual traits to be continuously replenished. BioEssays 27: 518–525, 2005. © 2005 Wiley periodicals, Inc.