Atherosclerosis (AS) has now been widely recognized as a complex and multifactorial disease that might be caused by a combination of various environmental, behavioral, physiologic, and genetic factors. Ginsengs and ginsenosides have been widely prescribed for the prevention and treatment of AS and other cardiovascular diseases in Asian countries, either alone or in combination. This chapter summarizes the experimental data that outline the evidence for ginsenosides as anti-atherosclerotic agents. It identifies the most effective components and the underlying mechanisms for regulating AS. Protective effects of ginsengs and/or corresponding ginsenosides on vascular endothelial cells and smooth muscle cells might be partly responsible for their therapeutic potential against AS. The paucity of rigorously designed, randomized, and/or controlled clinical trials limits the development of ginseng and/or ginsenosides for their full potential clinical therapeutic effects against AS. In addition, the specific molecular mechanisms underlying their preventative effects against AS need to be elucidated further.