Methanol and formate are attractive microbial feedstocks as they can be sustainably produced from CO2 and renewable energy, are completely miscible, and are easy to store and transport. Here, we provide a biochemical perspective on microbial growth and bioproduction using these compounds. We show that anaerobic growth of acetogens on methanol and formate is more efficient than on H2/CO2 or CO. We analyze the aerobic C1 assimilation pathways and suggest that new-to-nature routes could outperform their natural counterparts. We further discuss practical bioprocessing aspects related to growth on methanol and formate, including feedstock toxicity. While challenges in realizing sustainable production from methanol and formate still exist, the utilization of these feedstocks paves the way towards a truly circular carbon economy.