13 studies investigating the structural effects of substances believed to possess chondroprotective properties were included in this systematic review to determine whether patients with knee osteoarthritis (OA) would experience a delay in the progression of the disease. Treatments evaluated in this study included: oral glucosamine, chondroitin, nonsteroidal anti-inflammatory drugs (NSAIDs), polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamins (C, D, and E), intra-articular hyaluronic acid injections, and platelet-rich plasma (PRP). The findings indicated that chondroitin sulfate and glucosamine may reduce joint cartilage loss and thus delay the course of osteoarthritis. Results are conflicting for hyaluronic injections, and there is no evidence to support a chondroprotective effect of NSAIDs, vitamin D, or vitamin E.