Transcription Factor IIIA (TFIIIA) is specifically required for transcription of 5S ribosomal RNA, an essential component of the ribosome. The TFIIIA protein, found in every organism, has been characterized in several species. It shows remarkably poor conservation of primary protein sequence, but all orthologues analyzed carry several C2H2-zinc fingers that are required for TFIIIA binding to both 55 ribosomal DNA (rDNA) and RNA (rRNA). Alignments of TFIIIA protein and 55 rRNA gene sequences suggest a parallel evolution of the transcription factor and its natural binding site, the internal control region of the 5S rRNA gene. We discuss here how TFIIIA expression and availability in the cell is tightly regulated at the transcriptional, post-transcriptional and post-translational level to ensure adequate amounts of TFIIIA protein depending on cell type and developmental stage. This article is part of a Special Issue entitled: Transcription by Odd Pols. (C) 2012 Elsevier B.V. All rights reserved.