Cartilage lesions of the knee are common disorders affecting people of all ages; as the lesion progresses, it extends to the underlying subchondral bone and an osteochondral defect appears. Osteochondral (OC) tissue compromises soft cartilage over hard subchondral bone with a calcified cartilage interface between these two tissues. Osteochondral defects can be caused by numerous factors such as trauma and arthritis. Tissue engineering offers the possibility of a sustainable and effective treatment against osteochondral defects, where the damaged tissue is replaced with a long-lasting bio-manufactured replacement tissue. This review evaluates both bi-phasic and multi-phasic scaffold-based approaches of osteochondral tissue regeneration, highlighting the importance of having an interface layer between the bone and cartilage layer. The significance of a biomimetic approach is also evidenced and shown to be more effective than the more homogenous design approach to osteochondral scaffold design. Recent scaffold materials and manufacturing techniques are reviewed as well as the current clinical progress with osteochondral regeneration scaffolds.