AbstractCalcium sulfate (CS) has enjoyed a longer history of clinical use than most currently available biomaterials. It is well‐tolerated when used to fill bone defects and undergoes rapid and complete resorption without eliciting a significant inflammatory response. The raw material from which it is made is relatively inexpensive and abundant. In addition, CS can be used as a vehicle to deliver antibiotics, pharmacologic agents, and growth factors. It has found wide use in orthopedics and dentistry, and has been used in a variety of clinical applications, including the periodontal defect repair, the treatment of osteomyelitis, sinus augmentation, and as an adjunct to dental implant placement. Despite these advantages, the material has not enjoyed the popularity of many other regenerative materials, although there has been a recent resurgence of interest in the material. This review examines the properties and clinical applications of CS, with an emphasis on dental applications of the material. Limitations of the material are discussed as well as suggestions for future research. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009