The synthesis of mature and functional messenger RNA by eukaryotic RNA polymerase II (Pol II) is a complex, multistage process requiring the cooperative action of many cellular proteins. This process, referred to collectively as the transcription cycle, proceeds via five stages: preinitiation, initiation, promoter clearance, elongation, and termination. During the past few years, fundamental studies of the elongation stage of transcription have demonstrated the existence of several families of Pol II elongation factors governing the activity of Pol II. It is now clear that the elongation stage of transcription is a critical stage for the regulation of gene expression. In fact, two of these elongation factors, ELL and elongin, have been implicated in human cancer. This article will review the proteins involved in the regulation of the elongation stage of transcription by Pol II, describing the recent experimental findings that have propelled vigorous research on the properties and function of the elongating RNA polymerase II. --Shilatifard, A. Factors regulating the transcriptional elongation activity of RNA polymerase II.