The nucleosome and chromatin fiber provide the common structural framework for transcriptional control in eukaryotes. The folding of DNA within these structures can both promote and impede transcription dependent on structural context. Importantly, neither the nucleosome nor the chromatin fiber is a static structure. Histone dissociation, histone modification, nucleosome mobility, and assorted allosteric transitions contribute to transcriptional control. Chromatin remodeling is associated with gene activation and repression. Energy-dependent processes mediate the assembly of both activating and repressive proteins into the nucleosomal infrastructure. Recent progress allows the structural consequences of these processes to be visualized at the chromosomal level. DNA and RNA polymerase, SWI/SNF complexes, histone deacetylases, and acetyltransferases are targeted by gene-specific regulators to mediate these structural transitions. The mistargeting of these enzymes contributes to human developmental abnormalities and tumorigenesis. These observations illuminate the roles of chromatin and chromosomal structural biology in human disease.