The chromatin immunoprecipitation (ChIP) assay is a powerful method for probing protein-DNA interactions within the natural chromatin context of the cell is versatile enough for adaptation for a variety of purposes. This assay can be used to identify multiple proteins associated with a specific region of the genome, or the opposite, to identify the many regions of the genome associated with a particular protein. It has been exploited for mapping the localization of post-translationally modified histones and histone variants in the genome, and for mapping DNA target sites for transcription factors and other chromosome-associated proteins. It has emerged as technique of choice to investigate protein–DNA interactions inside the cell. The amalgamation of ChIP with high-throughput technologies like microarray and high-throughput sequencing has enabled the identification of protein-DNA interactions on a global scale. Several novel biological insights have emerged from protein-DNA interactions that have been identified using ChIP. This review highlights the principle and methodology of ChIP assay along with variants on the theme of the ChIP assay, and examples of their applications.