Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L.) are the two most recognized ginseng botanicals. It is believed that the ginseng saponins called ginsenosides are the major active constituents in both ginsengs. Although American ginseng is not as extensively studied as Asian ginseng, it is one of the best selling herbs in the US, and has garnered increasing attention from scientists in recent years. In this article, after a brief introduction of the distribution and cultivation of American ginseng, we discuss chemical analysis of saponins from these two ginsengs, i.e., their similarities and differences. Subsequently, we review pharmacological effects of the saponins, including the effects on the cardiovascular system, immune system, and central nervous system as well as the anti-diabetes and anti-cancer effects. These investigations were mainly derived from American ginseng studies. We also discuss evidence suggesting that chemical modifications of ginseng saponins would be a valuable approach to develop novel compounds in drug discovery.