Calcium sulphate has been used extensively as a bioabsorbable bone substitute for 90 years. Its advantages include its low cost, ready availability and unlimited supply, lack of donor site morbidity, use as a delivery vehicle for other compounds (especially antibiotics), inherent osteoconductive properties (based on a structure similar to bone), and its proven safety record. We sought to determine the evidence-based medical studies (prospective and/or randomized clinical trials) that support the use of calcium sulphate as a bioabsorbable bone substitute. At the present time, the majority of reports are basic science investigations, animal studies, and retrospective clinical reviews of varying degrees of quality. Multiple retrospective reviews reveal that calcium sulphate is an effective void-filler in contained bony defects such as metaphyseal voids after impacted fracture reduction (calcaneus, tibial plateau), simple bone cysts, or posttraumatic defects. Three case series examining the use of calcium sulphate in the treatment of bone nonunions revealed a significant failure rate, suggesting that this material, used in isolation, is not optimal to promote union in that setting. A low but consistent complication rate, specifically serous drainage from the wound as the calcium sulphate absorbs, has been reported. This complication is higher when the material is used in higher volumes (greater than 20 mL) or in subcutaneous bones (tibia, ulna). There is some Level I to II evidence (one randomized trial, one case-control study, one prospective cohort study) that antibiotic-impregnated bioabsorbable calcium sulphate has the potential to reduce the number of procedures and surgical morbidity associated with the surgical treatment of chronic osteomyelitis and infected nonunion while maintaining a high rate of infection eradication. Calcium sulphate remains an inexpensive, safe, reliable bone void filler that can also serve as a absorbable delivery vehicle for antibiotics or other compounds. Further high-quality randomized and prospective clinical trials are required to define the role of calcium sulphate in modern orthopaedics.