In eukaryotic cells, the main genetic information message is contained in the nuclei consisting of chromatin in which the ordered base sequence of the genes is organized as a DNA double-helical chain, wrapped around histone proteins to form polynucleosomal structures at various levels of condensation. These higher-order structures and conformations are affected by the interaction with numerous intracellular constituents (ions, proteins), with components of the external environment which indirectly modify the intracellular composition, and with many drugs added to influence the cellular machinery in a hopefully healthy manner, but often producing dramatic genetic deregulations. In this review we shall focus on some of the most important binding sites through which DNA may be attacked, resulting in structural alterations of this flexible macromolecule. In our laboratory, we have approached these problems essentially through the use of spectroscopic techniques, namely UV-Visible absorption and fluorescence spectroscopies, circular and electric linear dichroisms.