In humans, sexual dimorphism is associated with the presence of two X 
chromosomes in the female, whereas males possess only one X and a small and 
largely degenerate Y chromosome. How do men cope with having only a single X 
chromosome given that virtually all other chromosomal monosomies are lethal? 
Ironically, or even typically many might say, women and more generally female 
mammals contribute most to the job by shutting down one of their two X 
chromosomes at random. This phenomenon, called X-inactivation, was originally 
described some 50 years ago by Mary Lyon and has captivated an increasing number 
of scientists ever since. The fascination arose in part from the realisation 
that the inactive X corresponded to a dense heterochromatin mass called the 
"Barr body" whose number varied with the number of Xs within the nucleus and 
from the many intellectual questions that this raised: How does the cell count 
the X chromosomes in the nucleus and inactivate all Xs except one? What kind of 
molecular mechanisms are able to trigger such a profound, chromosome-wide 
metamorphosis? When is X-inactivation initiated? How is it transmitted to 
daughter cells and how is it reset during gametogenesis? This review retraces 
some of the crucial findings, which have led to our current understanding of a 
biological process that was initially considered as an exception completely 
distinct from conventional regulatory systems but is now viewed as a paradigm 
"par excellence" for epigenetic regulation.