Evidence to date has placed considerable emphasis on protein synthesis initiation as the dominant site of translational control. Two specific aspects are regulated, the binding of the initiator tRNA to the 40S subunits (as a ternary complex with eIF-2 and GTP) and the subsequent binding of mRNA to the complex of the 40S subunit with initiator tRNA. In addition to regulation, eIF-2 and Met-tRNAf are in large part responsible for selection of the initiating AUG codon. The utilization of most host mRNAs requires an m7G cap structure at the 5' end. However, many viral systems appear to use one of two alternate initiation schemes referred to as re-initiation and internal initiation. The function of specific initiation factors is presented and the consequences of altering the activity of these factors is discussed.