Proteins provide the structural framework of a cell and perform the enzymatic activities sustaining DNA replication and energy production. The hormones and growth factors that facilitate organ-to-organ communication are proteins as are the receptors and signaling intermediaries that integrate extracellular stimuli to intracellular action. As such, eukaryotic cells devote tremendous effort and energy to protein synthesis. The enzymes involved in protein synthesis have traditionally been described as cellular housekeepers. This was meant to imply that while they were necessary for cell viability, they were not thought to have a causal role in activating cell differentiation or neoplastic development the way that a transcription factor or hormone receptor might. However, two protein translation factors, protein initiation factor eIF4E and protein elongation factor eEF1A2, have been identified as important human oncogenes. This review summarizes recent work showing that protein initiation and elongation factors have important regulatory roles in cell growth, apoptosis, and tumorigenesis.