In this issue, Hanes et al. use ribosome display, a technology previously developed for generating diverse protein libraries, to evolve high-affinity antibodies in a cell-free system. Ribosome display involves transcription and translation of libraries in such a way that the transcript, ribosome, and protein product remain physically linked. In this study they applied the technology to evolve and affinity-mature a large synthetic naïve human single-chain antibody (scFv) library. First they translated the scFv library and selected scFvs that bound to insulin. Next the mRNA encoding the bound scFv—and still associated with it—was released and subjected to affinity maturation, which involved several more rounds of reverse transcription, error-prone PCR, translation, and selection. The procedure yielded scFvs with picomolar affinities in just a few days, and without use of a single living organism (see p. 1287).