American ginseng (Panax quinquefolius L.) is grown in some regions of the USA and Canada and marketed for its health promoting attributes. While cultivation of this plant species has taken place in North America for over 100 years, there are many challenges that need to be addressed. In this article, the current production method used by growers is described and the challenges and opportunities for research on this valuable plant are discussed. These include studies on pharmacological activity, genetic diversity within the species, genetic improvement of currently grown plants, molecular characterization of gene expression, and management of diseases affecting plant productivity. The current research developments in these areas are reviewed and areas requiring further work are summarized. Additional research should shed light on the nature of the bioactive compounds and their clinical effects, and the molecular basis of active ingredient biosynthesis, and provide more uniform genetic material as well as improved plant growth, and potentially reduce losses due to pathogens.