This chapter reviews the general transcription factors that are characterized by their ability to function in intimate association with RNA polymerase I1 and focuses on their roles in the preinitiation, initiation, and elongation stages of transcription by RNA polymerase II. Messenger RNA (mRNA) synthesis is a major site for the regulation of gene expression. Eukaryotic mRNA synthesis is an elaborate biochemical process catalyzed by multisubunit RNA polymerase II and controlled by the concerted action of a diverse collection of transcription factors that fall into at least three functional classes—namely, (1) DNA binding transactivators, (2) coactivators, and (3) the general transcription factors. Among the most striking features of the general transcription factors are their sheer number and rich functional diversity. Transcription initiation by RNA polymerase II is preceded by an assembly of polymerase and the general initiation factors into an active preinitiation complex at the core region of a class II promoter. RNA polymerase II preinitiation complexes assemble at many TATA and TATA-less core promoters by a common pathway. TFIIF is unique among RNA polymerase II general transcription factors because of its ability to function in both the initiation and elongation stages of transcription.