How can matter transition from the nonliving to the living state? The answer is essential for understanding the origin of life on Earth and for identifying promising targets in the search for life on other planets. Most studies have focused on the likely chemistry of RNA (1), protein (2), lipid, or metabolic "worlds" (3) and autocatalytic sets (4), including attempts to make life in the lab. But these efforts may be too narrowly focused on the biochemistry of life as we know it today. A radical rethink is necessary, one that explores not just plausible chemical scenarios but also new physical processes and driving forces.