This chapter reports on a systematic review of the literature of crenobalneotherapy in the management of knee OA. Crenobalneotherapy is defined as the spectrum of techniques based on mineral or tap water and its derivatives, as used in a medical context. We searched Medline using the following keywords: ‘‘spa therapy’’, ‘‘mud’’, ‘‘radon’’, ‘‘balneotherapy’’, and ‘‘hydrotherapy’’ in combination with ‘‘OA’’, ‘‘arthrosis’’, and ‘‘gonarthrosis’’. We also reviewed the reference lists of articles retrieved by the Medline search. All studies that compared crenobalneotherapy to any other intervention or to no intervention were selected, and a checklist was used to assess their internal validity, external validity and the quality of the statistical analysis. We analyzed separately some components of crenobalneotherapy and comparators and four types of outcome criteria (pain, function, stiffness and quality of life). We calculated standardized response mean. There is middle level evidence that “multiple mineral interventions” that combine two or more components of crenobalneotherapy are superior to no treatment, high level evidence that its combination with home exercises is superior to home exercises alone and low level evidence that it is superior to short wave. There is high level but conflicting evidence that water exercise is superior to no treatment. There is a high level of evidence that water exercise is similar to land based exercise (but the studies noted that it is better tolerated). There is middle level evidence that massage is superior to no treatment. There is low level and conflicting evidence that bathing in mineral water is superior to or similar to bathing in tap water and that mineral mud and bathing in mineral water is superior to hot water. The only study evaluating heat (heat sleeve vs regular sleeve) found no differences but was a pilot study with insufficient sample size. Crenobalneotherapy seems to improve, pain, function, stiffness and quality of life in lower limb OA. As a whole treatment, its efficacy has a high level of evidence but efficacy of each component has middle level (massage) and sometimes high but conflicting level of evidence (exercise in water). There is low level evidence that chemical composition of water has a clinical relevant effect. More studies with higher methodology quality and sufficient sample size are needed in these fields.