In many species, females possess two X chromosomes and males have one X chromosome. This difference is critical for the initial determination of sex. However, the X encodes many functions required equally in males and females; thus, X chromosome expression must be adjusted to compensate for the difference in dosage between the sexes. Distinct dosage compensation mechanisms have evolved in different species. A common theme in the Drosophila melanogaster and Caenorhabditis elegans systems is that a subtle alteration of chromatin structure may impose this modest, but vital adjustment of the X chromosome transcription level.