When Charles Darwin formulated his theory of sexual selection in The Descent of Man, and Selection in Relation to Sex, sex differences were understood largely in terms of morphology, physiology and behavior. Recent genomic studies have demonstrated that sex differences are apparent at the molecular level. In the Drosophila study system, `faster-male' evolution is widespread, as is indicated by enhanced rates of amino acid substitution for male-biased as compared to nonsex- and female-biased genes. While the role of intrasexual male competition has been highlighted in the interpretation of these observations, the alternative hypothesis that historical sex differences may account for these patterns has not been addressed. To address the alternative hypothesis that relative constraints account for `faster-male' evolution in Drosophila, multivariate matching techniques were used. Male and female-biased genes were matched with nonsex-biased genes on several sets of proposed confounders and male and female effects were estimated. Adjustment for confounding due to historical sex differences resulted in a significant decrease in estimates of male effects on rates of molecular evolution and marginal increase or no difference in female effect estimates. After adjustment, male and female effects on rates of molecular evolution were similar suggesting that `faster-male' evolution may be largely due to sex differences in the efficacy of selection given historical constraints, rather than to contemporary selection. Multi-species data derived from the application of high-throughput technology on multiple closely related species of Drosophila permits the modeling of traits on a phylogeny on a genome-wide scale. This framework is used to study the role of intersexual coevolution in affecting genome evolution. Ancestral inference on sex-dependent gene expression is used to empirically test theoretical expectations about how sex-biased gene expression should arise, to identify candidate genes involved in ongoing intersexual developmental conflict, and to study the role of expression evolution on the `demasculinization' of X chromosomes. Functional analysis of candidate genes suggests that enhanced selection on male secondary sexual traits may be a common source of sexually antagonistic developmental conflict in Drosophila. Modeling of transition dynamics among states of sex-biased gene expression for X-linked and autosomal-linked genes indicates that expression evolution can account for the underrepresentation of male-biased genes on the X chromosome. Analysis of transition dynamics for candidate genes provides support for the hypothesis that the `demasculinization' of X chromosomes in Drosophila is partially due to the effects of sexually antagonistic coevolution on the evolution of gene expression.