Protein synthesis is controlled at the level of translation initiation. Cells rapidly respond to environmental changes by disassembly of polysomes and recruitment of specific mRNAs from inactive ribonucleoprotein particles into polysomes active in translation. Recent insights have elucidated specific protein and RNA sequence interactions that are required to mobilize translation of selective mRNAs. The specificity of translational control provides a unique target to inhibit synthesis of specific polypeptides to control infectious disease as well as to control aberrant cell growth. In addition, greater understanding of the factors that limit protein synthesis is enabling the design of novel strategies to optimize protein expression and engineer host cells for enhanced growth and protein synthesis capacity.