It has been over a decade since oxidative enzymes were first used to degrade carbon-based nanomaterials (CBNs). Although enormous progress has been achieved in this field, many questions and problems remain unresolved that need to be answered to usher these materials toward their true destiny. Nanobioscience researchers now know that ignoring the biomolecular corona (BMC) in nanobiomedical studies, either inadvertently or intentionally, is by no means justified. However, a major drawback to progress is that BMC effects on CBN biodegradation have been omitted from a large number of studies. What's more, many studies in the field have eliminated the BMC source in the relevant experiments. Thus, the most critical question that one needs to probe is whether the BMC and its characteristics affect the biodegradability of CBNs? In this conceptual perspective paper, recent progress and significant research in CBNs biodegradation are summarized. Then, the importance of the BMC and its possible impacts on the biodegradation of CBNs are thoroughly explored as a conceptual guide. Finally, remaining challenges and the direction of future research are provided, and barriers that need to be overcome to advance the field are discussed including recommendations regarding BMC considerations and study design and reporting guidelines.