The present review focuses on the recent research developments in EPC biology, namely, (i) canonical and non-canonical SHH signaling pathways in EPCs and EC, related to homeostasis, (ii) SHH signal transmission by extracellular vesicles such as exosomes containing single-strand non-coding miRNAs and (iii) impaired SHH signaling in cardiovascular diseases. Here, SHH is linked to cardiovascular disorder.