The article highlights the current status of symptomatic slow-acting drugs (SYSADOA) in osteoarthritis (OA). Mechanism of action, clinical studies data on the effectiveness of glucosamine (GA) and chondroitin sulfate (CS) and their combinations in OA, their positive symptomatic and structural-modifying effects, are described. The article provides the latest recommendations for the OA treatment with these two drugs and presents an argument for the combination therapy with both drugs as a background therapy in the earliest stages of OA. It is indicated that such therapy should be long-term due to its high safety and possible reduction of cardiovascular accidents risk as well. It is noted that therapeutic doses of CS and GA are ≥1500 and ≥800 mg per day, respectively, and encapsulated forms of SYSADOAs have advantages due to their pharmacokinetic features.