Recent studies have challenged the view that transcription is predominantly regulated at the level of RNA polymerase II recruitment to promoters. Transcription is also regulated at the level of elongation by factors that act directly upon RNA polymerase II or that manipulate the chromatin environment. Hundreds of protein factors participate in transcription and its regulation in eukaryotes. Many of these proteins regulate specific genes by targeting upstream promoter regions, whereas a smaller but mechanistically diverse set of factors functions at most genes during RNA polymerase II (Pol II) elongation. These elongation factors can affect mRNA production at particular stages and in different ways during transcription. Some factors act directly on Pol II, whereas others manipulate the chromatin environment.