Bone graft materials which can induce and promote the bone regeneration have always been applied to replace damaged parts of the bone and restore the physiological functionality. Among these bone graft materials, calcium sulfate is one sort of bioactive materials with high biological activity, biocompatibility and biodegradability, which is applied widely for basic and clinical research. However, because of its fragility, low mechanical strength and fast degradation, there remains limitations when calcium sulfate is applied alone. Given that, more and more calcium sulfate composites have been developed to improve the disadvantages of the pure calcium sulfate. Good osteo-conductivity, osteo-inductivity and biocompatibility of bone graft materials are vital factors for an ideal clinical effect, so it’s very important to assess the osteogenesis and biocompatibility of calcium sulfate composites through either in-vivo or in-vitro studies. In the current review, calcium sulfate composites have a good osteo-conductivity, osteo-inductivity and biocompatibility and can be put into clinical use safely.