DNA-binding proteins control various cellular processes such as recombination, replication and transcription. This review is aimed to summarize some of the most commonly used techniques to determine DNA-protein interactions. In vitro techniques such as footprinting assays, electrophoretic mobility shift assay, southwestern blotting, yeast one-hybrid assay, phage display and proximity ligation assay have been discussed. The highly versatile in vivo techniques such as chromatin immunoprecipitation and its variants, DNA adenine methyl transferase identification as well as 3C and chip-loop assay have also been summarized. In addition, some in silico tools have been reviewed to provide computational basis for determining DNA-protein interactions. Biophysical techniques like fluorescence resonance energy transfer (FRET) techniques, FRET-FLIM, circular dichroism, atomic force microscopy, nuclear magnetic resonance, surface plasmon resonance, etc. have also been highlighted.