Nucleic acids are abundant biopolymers responsible for encoding, transmitting, and expressing genetic information. A milestone towards detail mechanistic understanding of biological functionality of nucleic acids is the characterization of their physiological structure and dynamics. There is a number of well­established biophysical techniques allowing characterization of nucleic acids in terma of their structure and/or dynamics including atomic­resolution methods such as X­ray diffraction (XRD) and solution nuclear magnetic resonance (NMR) spectroscopy. However, the structural information delivered by these methods often strongly depends on (subjectively chosen) experimental/environmental conditions and used instrumental setup. The consideration of the inherent sensitivity of nucleic acids structure to environmental factors has indicated that delineating of physiologically relevant quantitative structure­activity relationships for nucleic acids might only be possible with the use structural data derived under environmental conditions that are as close as possible to native conditions in vivo. Recently, number of methods has been developed for characterization of nucleic acid structure under physiological conditions in living cells. Here, I will illustrate potential of in­cell NMR spectroscopy for characterization of nucleic acid structure, stability, and interactions with drug like molecules in the native environment of the nuclei of living human cells