Cervical degenerative disc disease (CDDD) can lead to radiculopathy and myelopathy, resulting in pain, lack of function, and immobility. Anterior cervical discectomy and fusion (ACDF) is a common surgical treatment modality for advanced CDDD. ACDF involves removal of the affected disc(s) followed by replacement with a bone or synthetic graft. Historically, autograft has been considered the gold standard for interbody fusion. However, it is often associated with limitations, including donor site morbidity and limited quality and supply, prompting surgeons to seek alternatives. Two of the most common alternatives are structural bone allografts and polyetheretherketone (PEEK) synthetic cages. Both, advantageously, have similar mechanical properties to autologous bone, with comparable elastic modulus values. However, a lack of osseointegration of PEEK cages has been reported both pre-clinically and clinically. Reported fusion rates assessed radiographically are higher with the use of structural bone allografts compared to PEEK cages, while having a lower incidence of pseudarthrosis. This book chapter will discuss in detail the pre-clinical and clinical performance of structural allografts in comparison to conventional PEEK cages.