Heterocellular communication in the heart is an important mechanism for matching circulatory demands with cardiac structure and function, and neuregulins (Nrgs) play an important role in transducing this signal between the hearts' vasculature and musculature. Here, we review the current knowledge regarding Nrgs, explaining their roles in transducing signals between the heart's microvasculature and cardiomyocytes. We highlight intriguing areas being investigated for developing new, Nrg-mediated strategies to heal the heart in acquired and congenital heart diseases, and note avenues for future research.