Articular cartilage injuries are one of the most challenging problems in musculoskeletal medicine due to the poor intrinsic regenerative capacity of this tissue. The lack of efficient treatment modalities motivates research into tissue engineering: combining cells, biomaterials mimicking extracellular matrix (scaffolds) and microenvironmental signaling cues. The aim of this review is to focus on the use of biomaterials as delivery systems for microenvironmental cues in relation to their applications for treatment of cartilage defects. The latest advances in cartilage tissue engineering and regeneration are critically reviewed to demonstrate an outline of challenges toward biomaterial-based approaches of cartilage regeneration.