Untreated focal articular cartilage defects may lead to secondary osteoarthritis. Symptomatic full-thickness defects in young patients that are located in the medial or lateral femoral condyle, trochlea, or patella and range in size from 3 cm2 to 10 cm2 as well as defects of the ventral talus are indications for autologous chondrocyte transplantation (ACT). Another indication for ACT are cartilage defects for which previous operative measures have failed. Osteoarthritis and kissing lesions are contraindications. Axial malalignment and knee joint instability need to be corrected. Second-generation ACT procedures are based on three-dimensional biomaterials in which the articular chondrocytes are seeded prior to implantation. Randomized trials demonstrate clinical, radiographic, and histologic findings that are similar to marrow-stimulating techniques such as microfracture. Long-term studies are needed to determine the effect of ACT on the development of osteoarthritis.