Changes in the regulation of gene expression play a central role in evolution. Complexity and modes of regulation grew with the complexity of organisms. Among many changes, the number of transcription factors underwent expansion. The exaptation of transposable elements (TE) introduced new regulatory elements and significantly rewired the old ones. A noticeable phenomenon is the abundance of posttranscription regulatory mechanisms in metazoans and more complex organisms than unicellular organisms. Regulation by noncoding RNAs plays a significant role in multicellular organisms. Thus, the increasing complexity and abundance of various gene regulatory mechanisms drive the evolution of complex organisms.