In eukaryotes, transcription of the diverse array of tens of thousands of protein-coding genes is carried out by RNA polymerase II. The control of this process is predominantly mediated by a network of thousands of sequence-specific DNA binding transcription factors that interpret the genetic regulatory information, such as in transcriptional enhancers and promoters, and transmit the appropriate response to the RNA polymerase II transcriptional machinery. This review will describe some early advances in the discovery and characterization of the sequence-specific DNA binding transcription factors as well as some of the properties of these regulatory proteins.