The simple message of this paper is that it is the high time to reevaluate the strategies and optimize the efforts for investigation of thermal (spa) waters. Several articles trying to clear mode of action of medicinal waters have been published up to now. Almost all studies apply the unproven hypothesis, namely the inorganic ingredients are in close connection with healing effects of bathing. Change of paradigm would be highly necessary in this field taking into consideration the presence of several biologically active organic substances in these waters. A successful design for experimental mechanistic studies is approved.