Non-coding RNAs regulate dosage compensation in mammals by controlling transcriptional silencing of one of the two X chromosomes in females. The two major transcripts involved in this process are Xist and its antisense counterpart Tsix. Expression of Xist and Tsix from the X inactivation center is mutually exclusive. Xist expression triggers chromosome wide silencing of the X chromosome from which it is transcribed. Tsix is a repressor of Xist and is specifically expressed from the other X chromosome, maintaining its activity. Here, we review non-coding RNAs that have been implicated in X chromosome inactivation. Focusing on the best studied transcripts Xist and Tsix we portray a current perspective on chromosome wide gene regulation by non-coding RNAs.