Ginseng replant disease (GRD) has had a major impact on the American ginseng (Panax quinquefolius L.) industry in Canada and is a threat to its survival. With only 150 yr of domestic ginseng cultivation, GRD and its effect on the industry in North America is well documented compared with replant diseases in other crops. However, minimal research has been published on the etiology and management of GRD. Research and observations of replant diseases of the major commercial Panax species worldwide are presented to propose mechanisms of GRD and potential management options. The available evidence suggests the specific involvement of the soil-borne fungus Ilyonectria mors-panacis (A.A. Hildebr.) A. Cabral & Crous combined with an unknown host-related factor as the ultimate cause of GRD, since other proposed mechanisms seem unlikely to have occurred in the diversity of regions where GRD is reported. Other abiotic and biotic factors influencing the severity of the disease are also likely to be involved. Given the lack of clarity in the scientific literature between problems associated with continuous cultivation of ginseng and true replant disease, a definition of GRD is proposed. The development of an effective and economical management regime will require a better understanding of the mechanisms of GRD. Potential management options include reducing ginseng debris after harvest of the first crop, preplant testing to identify low-risk sites for replanting, fumigation, alternative disinfestation techniques, and fungicides (including biofungicides) targeting I. mors-panacis.