Introduction: Among the notable breakthroughs in the past two decades of research in natural drug discovery is the identification of saponins (saponins in Panax notoginseng, PNS) as the primary ingredient of Panax notoginseng, an iconic herbal medicine in East Asia. Increasing evidences suggest that PNS have versatile effects against a variety of cardiovascular diseases (CVDs), leading to four clinical trials completed and/or underway. There is a timely need to summarize our current understanding of these natural compounds. Areas covered: In this review, the authors summarize and critically appraise the latest literature (mainly since 2008), which study PNS as potential therapeutic agents against CVDs. Furthermore, they introduce the structures of major PNS types, analyze their cellular targets and associated signaling pathways and discuss the emerging opportunities for their clinical applications. A major focus here is on how these compounds affect the cardiovascular system via diverse mechanisms of action. Expert opinion: The authors believe that future research should head in two directions. The first direction taken should involve establishing a PNS compounds library to correlate their functions with structures; the second direction should be by integrating network pharmacology and pharmaceutical techniques in the future development of these natural compounds as new vascular medicine.