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Articular cartilage lesions are a commonly encountered medical problem, for which there exists no satisfactory solution at present. Although many treatment protocols are in current clinical use, few of these have been the subject of rigorous evaluation in animal studies. Such an evaluation requires not only the selection of a suitable animal species, but also careful consideration of the defect parameters, not per se, but in relation to the biologic setting, and of whether this model is of relevance when transposed to the human situation. The current study addresses some of the common pitfalls into which investigators unknowingly stumble and which, unless avoided, can render their studies less meaningful in the human context. Because most treatment protocols entail the deposition of a space filling matrix within the defect void, the important attributes which such a material should possess also are described in this article.