This systematic review aims to evaluate the available evidence from randomized clinical trials of the clinical efficacy and safety of ginseng. Systematic literature searches were performed in 13 databases up to March 2009 without language restriction. All randomized clinical trials evaluating the clinical effects or safety of the use of ginseng monopreparations (Panax ginseng or P. quinquefolium) were considered for inclusion. A total of 411 potentially relevant studies were identified and 57 randomized clinical trials were included. The main indications included glucose metabolism, physical performance, psychomotor function, sexual function, cardiac function, pulmonary disease, and cerebrovascular disease. We found strong evidence of a positive effect of ginseng on glucose metabolism, psychomotor function, and pulmonary disease, whereas evidence suggests that ginseng is not effective at enhancing physical performance. However, ginseng generally has a good safety profile and the incidence of adverse effects seems to be low. In conclusion, our review compiles the evidence on the use of ginseng, finding a strong positive potential for glucose metabolism, psychomotor function, and pulmonary disease, but not for physical performance enhancement.