To deliver biopharmaceutics, subcutaneous (SC) route surpasses intravenous (IV) route unequivocally in time and cost savings, but it has been limited by the injection volume of no greater than 2 mL for a long time. Recently, the adoption of hyaluronidase has become a plausible method to realize high-dose high-volume biopharmaceutical products for SC injection. Among the hyaluronidase family, the recombinant human PH20 appears to be the most reliable candidate with excellent efficacy and safety for co-formulation development. As of 2024, a total of eight hyaluronidase co-formulated biological products have been approved by regulatory authorities. This review article systematically summarized the commercial hyaluronidase co-formulated biopharmaceutics and highlighted the critical aspects of the development of future products regarding selection of hyaluronidase, formulation and process development, non-clinical evaluation, and clinical investigation. Of note, considering the uniqueness of each therapeutic agent, early and effective communication with regulatory authorities is of vital importance to successful development. Discussions were further Expanded to cover the combination of hyaluronidase co-formulations with large-volume handheld autoinjectors. The ultimate goal of this review is to provide a practical and comprehensive reference that will substantially contribute to the development of hyaluronidase co-formulated biopharmaceuticals, thereby advancing the field and benefiting patients worldwide.