The assembly of macromolecular structures consisting of proteins and DNA lies at the core of many fundamental cellular processes, such as transcription, recombination and replication. A common theme to all these processes is DNA looping, which provides the backbone for the required long-range interactions on DNA and results in further complexity that is exceptionally difficult to tackle with traditional quantitative approaches. Here, recent advances in mathematical and computational methods to study the assembly of protein-protein/DNA complexes with loops and their effects in the cellular behaviour through gene regulation are reviewed. The interplay between multisite DNA looping and DNA bending regulatory proteins, such as the catabolite activator protein (CAP), and on its physiological consequences is focused on. It has become clear in the last few years that the complexity that looping brings about can actively control transcriptional noise and cell-to-cell variability. Here, it is shown that the DNA looping, through the effects of CAP, can also control the balance between robustness and sensitivity of the induction of gene expression.