Synthetic and natural biomaterials are a promising alternative for the treatment of critical-sized bone defects. Several parameters such as their porosity, surface, and mechanical properties are extensively pointed out as key points to recapitulate the bone microenvironment. Many biomaterials with this pursuit are employed to provide a matrix, which can supply the specific environment and architecture for an adequate bone growth. Nevertheless, some queries remain unanswered. This review discusses the recent advances achieved by some synthetic and natural biomaterials to mimic the native structure of bone and the manufacturing technology applied to obtain biomaterial candidates. The focus of this review is placed in the recent advances in the development of biomaterial-based therapy for bone defects in different types of bone. In this context, this review gives an overview of the potentialities of synthetic and natural biomaterials: polyurethanes, polyesters, hyaluronic acid, collagen, titanium, and silica as successful candidates for the treatment of bone defects.