Non coding RNAs have provided in the last decades a very exciting research field with the discovery that a largely unexplored fraction of our genome encodes for RNA without protein coding activity. Here we revise the current knowledge of how non coding RNAs impact on muscle differentiation and homeostasis in normal and disease conditions and how they can provide powerful tools for therapeutic interventions and disease diagnosis. Moreover, we discuss new insights into additional mechanisms of post-transcriptional regulation involving a new class of long non coding RNAs shown to impact on the distribution of microRNA molecules on their mRNA targets.