CRISPR activation and interference (CRISPRa/i) technology offers the unprecedented possibility of achieving regulated gene expression both in vitro and in vivo. The DNA pairing specificity of a nuclease dead Cas9 (dCas9) is exploited to precisely target a transcriptional activator or repressor in proximity to a gene promoter. This permits both the study of phenotypes arising from gene modulation for investigative purposes, and the development of potential therapeutics. As with virtually all other organ systems, the cardiovascular system can deeply benefit from a broader utilisation of CRISPRa/i. However, application of this technology is still in its infancy. Significant areas for improvement include the identification of novel and more effective transcriptional regulators that can be docked to dCas9, and the development of more efficient methods for their delivery and expression in vivo.