Biogas produced by anaerobic digestion is an important renewable energy carrier. Nevertheless, the high CO2 content in biogas limits its utilization to mainly heat and electricity generation. Upgrading biogas into biomethane broadens its potential as vehicle fuel or substitute for natural gas. CO2-to-CH4 bioconversion represents one cutting-edge solution for biogas upgrading. In-situ bioconversion can capture endogenous CO2 directly from the biogas reactor, is easy to operate, and provides an infrastructure for renewable electricity storage. Despite these advantages, several intrinsic challenges need to be addressed to move in-situ upgrading technologies closer to applications at scale. This opinion article reviews the state-of-art of this technology and identifies some obstacles and opportunities of biological in-situ upgrading technologies for future development.