Electron micrographs first confirmed that the eukaryotic genome is organized into repeating disk-shaped nucleosomal units composed of histones and their associated DNA. Those images made clear the function of the nucleosome in packaging and condensing the genome. Today, nucleosomes are recognized as highly dynamic units through which the eukaryotic genome can be regulated with epigenetically heritable consequences. This review focuses on the conserved protein structures that mobilize and remodel nucleosomes and specifically mark and recognize their histone and DNA components. These events directly impact DNA transcription, replication, recombination, and repair.