The evolution of antibiotic resistance can now be rapidly tracked with high-throughput technologies for bacterial genotyping and phenotyping. Combined with new approaches to evolve resistance in the laboratory and to characterize clinically evolved resistant pathogens, these methods are revealing the molecular basis and rate of evolution of antibiotic resistance under treatment regimens of single drugs or drug combinations. In this Progress article, we review these new tools for studying the evolution of antibiotic resistance and discuss how the genomic and evolutionary insights they provide could transform the diagnosis, treatment and predictability of antibiotic resistance in bacterial infections.