The human genome regulates dynamic patterns of transcript expression and while studies in recent years by the Encyclopedia of DNA Elements (ENCODE) consortium have shown the remarkable complexity of pervasive transcription, it is estimated that less than 2 % of the genome codes for proteins. Multiple lines of experimental evidence now highlight the functional importance of noncoding RNAs (ncRNAs) that serve to control transcription that underlie development and homeostatic control in metazoans. An emerging theme is the modulation of transcription factor binding governed by ncRNA-chromatin interactions. Some of the recent discoveries of contractile function in the heart implicate novel roles for long ncRNAs (lncRNAs), including the primary microRNA-208b (Pri-miR-208b) as well as antisense β-MHC (AS β-MHC). As such, this review will focus on the signaling and regulatory functions of ncRNAs that ensure homeostasis of mammalian myosin motor protein expression and cardiovascular disease.