X chromosome inactivation is a mechanism that modulates the expression of X-linked genes in eutherian females (XX). Ohno proposed that to achieve a proper balance between X-linked and autosomal genes, those on the active X should also undergo a 2-fold upregulation. Although some support for Ohno's hypothesis has been provided through the years, recent genomic studies testing this hypothesis have brought contradictory results and fueled debate. Thus far, there are as many results in favor as against Ohno's hypothesis, depending on the nature of the datasets and the various assumptions and thresholds involved in the analyses. However, they have confirmed the importance of dosage balance between X-linked and autosomal genes involved in stoichiometric relationships. These facts as well as questions and hypotheses are discussed below.