Errors in protein synthesis disrupt cellular fitness, cause disease phenotypes and shape gene and genome evolution. Experimental and theoretical results on this topic have accumulated rapidly in disparate fields, such as neurobiology, protein biosynthesis and degradation and molecular evolution, but with limited communication among disciplines. Here, we review studies of error frequencies, the cellular and organismal consequences of errors and the attendant long-range evolutionary responses to errors. We emphasize major areas in which little is known, such as the failure rates of protein folding, in addition to areas in which technological innovations may enable imminent gains, such as the elucidation of translational missense error frequencies. Evolutionary responses to errors fall into two broad categories: adaptations that minimize errors and their attendant costs and adaptations that exploit errors for the organism’s benefit.