We are dependent on our cardiovascular system for life support. Defects in the formation of either the heart or vasculature can be fatal in utero, reflecting our dependency on this system from almost the earliest stages of life. The cardiovascular system is remarkably stereotypical in its structure, both between individuals and across species. This demonstrates that a strict genetic programme dictates this structure and that the programme is conserved. Focussing primarily on the early stages of heart development, we utilise the zebrafish model for its genetic tractability to identify regulators of cardiovascular development. Using forward genetics, we have discovered several novel regulators of cardiac and vascular development. One such regulator is a novel Hyaluronidase, named Cemip2 (formerly Tmem2), that is required for both cardiac development and angiogenesis. Early data suggests that the function of this protein is conserved in mammals. We have also identified a regulator of N-cadherin trafficking and show that it is required for cardiomyocyte cell adhesion. Whilst exciting for discovery’s sake, this fundamental knowledge is essential for understanding inherited cardiovascular diseases and in plying our knowledge to devise therapeutic strategies.