Cartilage is considered to be a simple tissue that should be easy to engineer because it is avascular and contains just one cell type, the chondrocyte. Despite this apparent simplicity, regenerating cartilage in a form that can function effectively after implantation in the joint has proven difficult. This may be because we have not fully appreciated the importance of different structural regions of articular cartilage or of understanding the origins of chondrocytes and how this cell population is maintained in the normal tissue. This review considers what is known about different regions of cartilage and the types of stem cells in articulating joints and emphasizes the potential importance of regeneration of the lamina splendens at the joint surface and calcified cartilage at the junction with bone for long-term survival of regenerated tissue in vivo.