The formation of DNA loops by proteins and protein complexes is ubiquitous to many fundamental cellular processes, including transcription, recombination and replication. Recently, advances have been made in understanding the properties of DNA looping in its natural context and how they propagate to cellular behavior through gene regulation. The result of connecting the molecular properties of DNA looping with cellular physiology measurements indicates that looping of DNA in vivo is much more complex and easier than predicted from current models, and reveals a wealth of previously unappreciated details.