Salt ions and water present in living cells are essential mediators of protein-nucleic acid interactions. X-ray scattering and computational methods are applied to study the ion distributions around double-helical DNA, and to understand the complex electrostatic interactions that modulate single-stranded DNA conformation in solution. The spatial distributions and numbers of ions are measured and compared with theoretical predictions. X-ray data for single-stranded DNA reveal ion- and sequence-dependent properties of the conformational ensembles that support recent predictions of polyelectrolyte theory and provide a structural basis for the mechanical properties of these nucleic acids. The data presented here also identify shortcomings of current electrostatic theory and molecular dynamics force fields for modeling DNA in solution, and suggest how they may be improved. Finally, cryo-cooling methods are developed for xray scattering that provide unique advantages for high throughput structural investigations of biomolecules.