Spa therapy represents a popular treatment for many rheumatic diseases. The mechanisms by which immersion in mineral or thermal water or the application of mud alleviates suffering in rheumatic diseases are not fully understood. The net benefit is probably the result of a combination of factors, with mechanical, thermal and chemical effects among the most prominent ones. Buoyancy, immersion, resistance and temperature all play important roles. According to the gate theory, pain relief may be due to the pressure and temperature of the water on skin; hot stimuli may influence muscle tone and pain intensity, helping to reduce muscle spasm and to increase the pain threshold. Mud-bath therapy increases plasma β-endorphin levels and secretion of corticotrophin, cortisol, growth hormone and prolactin. It has recently been demonstrated that thermal mud-pack therapy induces a reduction in the circulating levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), important mediators of inflammation and pain. Spa therapy has been found to cause an increase in insulin-like growth factor-1 (IGF1), which stimulates cartilage metabolism, and transforming growth factor-β (TGF-β). There is also evidence of the positive action of mud-packs and thermal baths on the oxidant/antioxidant system, with a reduction in the release of reactive oxygen (ROS) and nitrogen (RNS) species. Overall, thermal stress has an immunosuppressive effect. Many other non-specific factors may also contribute to the beneficial effects observed after spa therapy in some rheumatic diseases, including effects on cardiovascular risk factors, and changes in the environment, pleasant surroundings and the absence of work duties.