A number of clinical series have described the effect of meniscus allograft replacement in humans. The general indication has been disabling pain following loss of a meniscus in a skeletally mature individual. Overall, healing of the graft to the capsule occurs in up to 80% of all transplants. Revascularization and cell repopulation is found in all grafts but is highly variable. The risk for graft failure seems to be greater with irradiated grafts and in patients with grade III or IV osteoarthritic changes. In most series, patients experienced a decrease in pain and an increase in activity level postoperatively. In many series, concominant surgery (cruciate ligament reconstruction or osteotomy) had been performed. Meniscus replacement with frozen or cryopreserved allografts seems to give the most promising short-term results in patients with post-meniscectomy pain. Controlled, randomized prospective studies are needed to confirm a long-term benefit and better define transplantation indications. Viable meniscus allografts seem to survive transplantation, as donor cells were found in the graft after 2 years. Clinically, pain was reduced and activity increased following transplantation, but after 4 years some of these gains were lost. There was no correlation between postoperative findings on MRI and clinical outcome. Meniscal replacement with a quadriceps tendon autograft in humans resulted in pain reduction, but at second-look arthroscopy, only 2 of 9 tendon autografts looked like a meniscus. Six were in position but still looked like tendons. Total medial meniscus replacement by quadriceps tendon autrograft is still an experimental procedure. There is no proof at present that meniscal substitutes (meniscus allografts or tendon autografts) in humans can protect the hyaline cartilage of the knee from the degeneration, following loss of a meniscus. There is some evidence in animal experiments that under circumstances not yet exactly known, a meniscus substitute can have a protective effect on articular cartilage. Three factors have been identified that prevent proper meniscal function: poor fixation of the meniscal horns, no contact of the graft with the articulating surfaces under load and incorrect positioning of the horns. Meniscal allograft transplantation sensitizes humoral and cell mediated immune systems. Bone plugs attached to meniscal allograft tissue may increase cell surface antigenicity. Deep freezing and especially freeze drying of meniscal tissue decreases host immunogenicity. Cryopreservation maintains the content of donor HLA encoded antigens and is likely more sensitizing to the host. The clinical importance of immune responses to meniscal allografts is not known, but it has not been shown to result in graft failure or rejection. Prospective studies are needed.