Osteobiologics are defined as a group of natural and synthetic materials used to augment bone healing. The selection of the most appropriate osteobiologic from the growing list of available options can be a challenging task. In selecting a material, surgeons should weigh a variety of considerations, including the indication for their use (the when), the most suitable substance (the what), and the correct mode of application (the how). This summary reviews these considerations and seeks to provide the surgeon with a basis for informed clinical evidence-based decision-making in their choice of a successful option.