In regenerative approaches, scaffolds play a crucial role in defining the 3-D anatomical shape and microenvironment for regenerative cells, while maintaining space, favoring regeneration of new bone, and preventing soft tissue migration in the bony lesion. A variety of materials have been explored as scaffolds for bone tissue regeneration. Metals are generally inappropriate for such applications because they lack the desired degradability in a biological environment requiring a second surgery. Synthetic polymers can provide physical strength and engineered chemical properties however, they do not have optimal ease of handling or predictable biodegradation rate. In contrast to these scaffolds, calcium sulfate, also known as Plaster of Paris, is a highly biocompatible and biodegradable material that is one of the simplest synthetic bone-like grafts. It has been sued as a graft material in orthopedics and dentistry for more than one hundred years. The present review illustrates and examines current advances regarding calcium sulfate sources, various properties,scaffold forms, and clinical applications for bone tissue engineering.Additionally,it also describesNanocrystallinecalcium sulfate. Keywords: Calcium sulfate; Gypsum; Plaster of Paris; Graft; Regeneration