Management of degenerative spine pathologies frequently leads to the need for spinal fusion, where bone growth is induced towards stabilization of the interventioned spine. Autologous bone graft (ABG) remains the gold standard inducer, while new bone graft substitutes attempt to achieve effective de novo bone formation and solid fusion. Limited fusion outcomes have driven motivation for more sophisticated and multidisciplinary solutions, involving new biomaterials and/or biologics, through innovative delivery platforms. The present review will analyze the most recent body of literature focused on new approaches for consistent bone fusion of spinal vertebrae, including the development of new biomaterials that pursue physical and chemical aptitudes; the delivery of growth factors (GF) to accelerate new bone formation; and the use of cells to improve functional bone development. Bone graft substitutes currently in clinical practice, such as demineralized bone matrix and ceramics are still used as starting point for study of new bioactive agents. Polyesters such as polycaprolactone and polylactic acid arise as platforms for development of composites, where a mineral element and cell/growth factors constitute the delivery system. Exciting fusion outcomes were obtained in several small and large animal models with these. On what regards bioactive agents, mesenchymal stem cells, preferentially derived from the bone marrow or adipose tissue, were studied in this context. Autologous and allogeneic approaches, as well as osteogenically differentiated cells, have been tested. These cell sources have further been genetically engineered for specific growth factor expression. Nevertheless, results on fusion efficacy with cells have been inconsistent. On the other hand, delivery of growth factors (most commonly BMP‐2), have provided favorable outcomes. Complications related to burst release and dosing are still target of research through development of controlled release systems or alternative GF such as NELL‐1, Oxysterols or COMP‐Ang1. Promising solutions with new biomaterial and GF compositions are becoming closer to the human patient, as these evidence high fusion performance, while offering cost and safety advantages. The use of cells has not yet proven solid benefits, whereas further understanding of cell behavior remains a challenge.