Emerging evidence has pointed to the importance of long non-coding RNAs (lncRNAs) in biological function and disease. However, lncRNAs remain largely unexploited in the vascular system. In this issue of ATVB, Zhao et al., identified a novel vascular smooth muscle cell-specific lncRNA, Myoslid. The investigators demonstrated that Myoslid, whose expression is transcriptionally controlled by SRF and myocardin, regulates smooth muscle cell proliferation and differentiation program, at least in part, by modulating the TGF-β pathway. This study has uncovered the involvement of non-coding RNAs in the already complicated gene regulatory networks in vascular biology, highlighting the potential of lncRNAs as novel therapeutic targets for cardiovascular disorders.