Medical-grade calcium sulfate has been successfully used for several decades as a bone filler and as a carrier with medications or bone growth factors for the treatment of bone defects. The present review illustrates the biological behavior and clinical outcomes of this material when used in clinical implant dentistry. Furthermore, the review illustrates the different indications specifically related to implant dentistry when medical-grade calcium sulfate has been used alone or in combination with bone grafting materials. The histological published evidence is reviewed together with successful clinical results. This material, well known since the 1800's, continues to be used by clinicians and researchers worldwide, and the latest scientific evidence clearly indicates that medical-grade calcium sulfate can be used alone or in combination with biologically active proteins in applications such as socket preservation, ridge augmentation, and sinus lift procedures.