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The various Rheumatology/Osteoarthritis Societies (the American College of Rheumatology, the Arthritis Foundation, the European League Against Rheumatism, the National Institute for Health and Care Excellence, the European society for clinical and economic aspects of osteoporosis and osteoarthritis, and the Italian consensus on appropriateness of osteoarthrosis therapies) published specific recommendations for the management of osteoarthrosis affecting hand, hip and knee. These evidence-based guidelines take into account safety and tolerability of pharmacological and non-pharmacological interventions available from the scientific literature as well as the opinions of the clinical specialists to provide complete, clear and transparent recommendations for the management of osteoarthrosis. This article provides an update of the scientific literature for selected treatments of osteoarthrosis focusing on the therapy with symptomatic slow-acting drugs (SYSADOAs) and disease modifying anti-osteoarthrosis drugs (DMOADs) (chondroitin sulfate, glucosamine, diacerein, unsaponifiable soy and avocado extracts). Moreover, the management of osteoarthrosis pain and function, avoidance of adverse events and long-term outcomes by SYSADOAs/DMOADs molecules is considered. Finally, based on the real-world data, the opinion of the various Rheumatology/Osteoarthritis Societies of all over the word is illustrated and discussed also by considering the structure, quality and properties of the SYSADOAs/DMOADs agents used in the treatment of osteoarthrosis. In particular, the results reported in numerous studies are contradictory and not always convincing about the efficacy of chondroitin sulfate and glucosamine as SYSADOAs and DMOADs. The cause of these non-homogeneous results could be due to the use in different studies of chondroitin sulfate and glucosamine preparations of varying quality. It is therefore mandatory to carry out new clinical studies using chondroitin sulfate and glucosamine of pharmaceutical grade or of the best possible quality to ascertain their usefulness as biomolecules in the treatment of osteoarthrosis.