This chapter provides a comprehensive evaluation of the biocompatibility of graphene-based materials (GBMs), with a particular focus on their interactions with biological systems and their potential in biomedical applications. Emphasis is placed on understanding how physicochemical properties—such as surface chemistry, functionalisation, morphology, and dispersibility—influence cellular responses, biodistribution, and overall toxicological profiles. Key advances in tissue engineering are explored, highlighting how GBMs can support stem cell differentiation, promote tissue regeneration, and serve as scaffolds for complex biological architectures. The text draws on a wide range of both in vitro and in vivo studies to illustrate the nuanced and sometimes contradictory findings regarding cytotoxicity, immunogenicity, and long-term integration in living systems. Ongoing challenges, including standardisation of testing protocols, dose-dependent effects, and long-term safety, are critically examined. The discussion aims to clarify the current limitations while identifying promising strategies for enhancing the biocompatibility and functional performance of GBMs in clinical settings. By situating GBMs at the intersection of nanotechnology and regenerative medicine, this chapter contributes to a growing body of knowledge essential for the safe and effective deployment of advanced materials in biomedical engineering.