Translational control of gene expression is an important regulatory mechanism in cellular physiology. In eukaryotes, ribosomes can initiate translation by two different mechanisms: a majority of mRNAs undergo cap-dependent initiation at their extreme 5'-ends, but initiation can occur internally in some mRNAs. A number of important cellular responses, such as entry into a proliferative state and adaptation to changing nutrient levels, are mediated by changes in the mechanism of translation initiation of specific mRNAs. This article discusses new insights into control of gene expression gained through studies of regulation of eukaryotic translational initiation.