The term “symptomatic slow-acting drugs for osteoarthritis” (SySADOA) was coined more than a decade ago to designate medications and/or nutritional supplements used to alleviate the manifestations of osteoarthritis in the long-term. Their efficacy has always been a focus of considerable skepticism. However, a critical reappraisal of the available data, which include results of carefully designed clinical trials conducted in accordance with Good Clinical Practice guidelines, strongly suggests a therapeutic effect. The effects of SySADOA need to be determined based, in particular, on treatment objectives (symptom relief, decreased use of nonsteroidal antiinflammatory drugs and other conventional agents, decreased radiographic progression, and decreased use of joint replacement surgery). In addition, the characteristics of the patients who are most likely to benefit from SySADOA need to be identified.