Precise spatio-temporal control of gene activity is essential for organismal development, growth, and survival in a changing environment. Decisive steps in gene regulation involve the pausing of RNA polymerase II (Pol II) in early elongation, and the controlled release of paused polymerase into productive RNA synthesis. Here we describe the factors that enable pausing and the events that trigger Pol II release into the gene. We also discuss open questions in the field concerning the stability of paused Pol II, nucleosomes as obstacles to elongation, and potential roles of pausing in defining the precision and dynamics of gene expression.Cell type-and condition-specific patterns of gene expression involve tight control of multiple steps in the transcription cycle. Early regulatory events govern the association of DNA-binding transcription factors (TFs) with their target motifs and the recruitment of RNA polymerase II (Pol II) and general TFs (GTFs) to the promoter region of a gene. These events enable transcription initiation and the synthesis of a short, nascent RNA. However, Pol II then pauses promoter-proximally, awaiting further signals before entering the gene body. The fate of the paused early elongation complex is absolutely decisive for gene output. If paused Pol II successfully transitions into productive elongation, a functional full-length mRNA can be made. However, a failure in the maturation of paused Pol II toward productive RNA synthesis short circuits the process of gene expression. Thus, understanding the factors that govern stable Pol II pausing and release are of paramount importance toward an appreciation of gene regulation in human health and disease.