This paper represents the text of two lectures given on the occasion of a Workshop on the X-Chromosome held at Hacettepe University, Ankara, in September 1994. The history of the development of ideas concerning the mechanism of X-chromosome inactivation is traced from the finding of the sex chromatin body in 1949. Important recent findings concern the Xist gene, which is a candidate gene for the X-inactivation center, from which inactivation is initiated. These recent findings shed new light on the abnormalities seen in human patients with X-linked genetic diseases or with aneuploidy of the X-chromosome.