Frequencies of synonymous codons are typically non-uniform, despite the fact that such codons correspond to the same amino acid in the genetic code. This phenomenon, known as codon bias, is broadly believed to be due to a combination of factors including genetic drift, mutational effects, and selection for speed and accuracy of codon translation; however, quantitative modeling of codon bias has been somewhat elusive. I will present a biophysical model which explains genome-wide codon frequencies observed across 20 organisms. Our model implements detailed codon-level treatment of mutations and includes two contributions to codon fitness which describe codon translation speed and accuracy. We find that the observed patterns of genome-wide codon usage are consistent with a strong selective penalty for mistranslated amino acids, while the dependence of codon fitness on translation speed is much weaker on average. Treating the translation process explicitly in the context of a finite ribosomal pool has allowed us to highlight the biophysical underpinnings of codon-level selective pressures. Overall, our approach offers a unified biophysical and population genetics framework for understanding the origin of codon bias.