In many organisms, females have two X chromosomes whereas males have just one. This natural X chromosome monosomy is not lethal, because of dosage compensation. Although numerous elegant genetic, biochemical and cytological experiments have been used to build up the mechanistic framework describing this specialized transcriptional control, dosage compensation is a chromosome-wide regulatory mechanism and is best studied at that level. Microarray techniques give us the chance to look simultaneously at the expression of all the genes in response to dose. These approaches have resolved old controversies, suggested new questions, and promise to give us a more clear and comprehensive understanding of an old problem in molecular and cell biology.