Among all the biomaterials introduced in the field of bone tissue engineering, injectable platelet-rich fibrin (I-PRF) has recently gained considerable attention. I-PRF, as a rich source of biologically active molecules, is a potential candidate which can be easily obtained in bedside and constitutes several biological factors which can result in higher anti-bacterial, anti-inflammatory and regenerative capabilities. According to the studies evaluating the osteogenic efficacy of I-PRF, this biomaterial has exhibited favorable outcomes in terms of adhesion, differentiation, migration, proliferation and mineralization potential of stem cells. In addition, the injectability and ease-of-applicability of this biomaterial has led to its various clinical applications in the oral and maxillofacial bone regeneration such as ridge augmentation, sinus floor elevation, cleft palate reconstruction and so on. Furthermore, to enhance the clinical performance of I-PRF, albumin gel-PRF as a long-lasting material for long-term utilization has been recently introduced with a gradual increase in growth factor release pattern. This review provides a comprehensive approach to better evaluate the applicability of I-PRF by separately appraising its performance in in-vitro, in-vivo and clinical situations. The critical approach of this review toward the different production protocols and different physical and biological aspects of I-PRF can pave the way for future studies to better assess the efficacy of I-PRF in bone regeneration.