The traditional route to investigating biology by perturbing living systems or by individually purifying and characterizing component parts is giving way to more complex endeavors where chemists and physicists attempt to build cells from scratch. Parallel efforts are underway that either exploits extant biological parts or prebiotically plausible molecules. Both approaches help to reveal the underlying physical–chemical forces that give rise to cellular function and highlight the important role played by polymers in regulating biological chemical systems. Although the success in RNA and lipid chemistry has led to the reconstitution of specific facets of cellular life, our understanding of dynamic, dissipative networks is currently too incomplete to allow for the construction of a self-sustained, integrated protocell. However, the presence of shared chemistry points to a promising path forward. Impact statement Advances in the understanding of the biophysics of membranes, the nonenzymatic and enzymatic polymerization of RNA, and in the design of complex chemical reaction networks have led to a new, integrated way of viewing the shared chemistry needed to sustain life. Although a protocell capable of Darwinian evolution has yet to be built, the seemingly disparate pieces are beginning to fit together. At the very least, better cellular mimics are on the horizon that will likely teach us much about the physicochemical underpinnings of cellular life.