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Tissue engineering aims to induce tissue self-regeneration in vivo or to produce a functional tissue replacement in vitro to be then implanted in the body. To produce a viable and functional tendon, the generation of a uniaxially orientated collagen type I matrix is required. Biochemical and physical factors can potentially alter both the production and the organization of this matrix, and their combination in a dose and time-dependent manner is probably the key to in vitro engineered tendons. This review discusses the role of these different factors affecting tenocytes growth in three-dimensional environment in vivo and in vitro, and underlines the future challenge of tendon tissue engineering