Historically, amino acids have been viewed as precursors for protein synthesis as well as metabolic substrates. Recently, a new role for amino acids as regulators of mRNA translation has been identified. In this role, they modulate the phosphorylation state of proteins that represent important control points in translation initiation, including the translational repressor 4E-BP1 and the ribosomal protein S6 kinase S6K1. When administered orally to fasted rats the branched-chain amino acids are particularly effective in stimulating translation initiation. Of the branched-chain amino acids, leucine is most potent. Interestingly, leucine administration stimulates global rates of protein synthesis in skeletal muscle but not in liver. However, in liver, branched-chain amino acids enhance the translation of a particular set of mRNAs typified by those encoding the ribosomal proteins and translation elongation factors, suggesting that branched-chain amino acids upregulate the capacity of the tissue to synthesize protein.