Historically the function of biomaterials was to replace diseased or damaged tissues. First generation biomaterials were selected to be as bio-inert as possible and thereby minimize formation of scar tissue at the interface with host tissues. Bioactive glasseswere discovered in 1969 and provided for the first time an alternative; strong, stable interfacial bonding of an implant with host tissues. In the 1980’s it was discovered that bioactive glasses could be used in particulae form to stimulate osteogenesiswhich thereby led to the concept of regeneration of tissues. This article summarizes the four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglassr. The four eras are; A) Era of Discovery, B) Era of Clinical Application, C) Era of Tissue Regeneration, and D) Era of Innovation. Key scientific and technological questions answered for the first three eras are presented. Questions still to be answered for the fourth era are included to stimulate innovation in the field.