The term adaptogen has not yet been accepted in medicine. This is probably due to the difficulties in discriminating adaptogenic drugs from immunostimulators, anabolic drugs, nootropic drugs, and tonics. There can be not doubt, however, that, at least in animal experiments, there are plant drugs capable of modulating distinct phases of the adaptation syndrome as defined by Seyle. These drugs either reduce stress reactions in the alarm phase or retard / prevent the exhaustion phase and thus provide a certain degree of protection against long-term stress. The small number of drugs the antistress activity of which has been proven or reported includes, among others, the plant drugs Ginseng, Eleutherococcus, Withania, Ocimum, Rhodiola, and Codonopsis. This review summarizes the major findings of pharmacological tests and human studies carried out with these drugs. Currently used assay systems allowing detection of antistress activities are also reported. At present the most likely candidates responsible for the putative antistress activity of plant drugs are special steroids, phenylprogane compounds and lignanes, respectively. Apart from influencing activities of the pituitary-adrenal axis and inducing stress proteins, many adaptogens also possess immunomodulatory and / or anabolic activities.