The effect of epigenetic modifications on the regulation of gene expression and the concomitant relationship to human diseases has become a key area of biological research in recent years. Studies have suggested that there is direct correlation between epigenetic modifications, such as histone methylation, histone acetylation and DNA methylation, and gene expression in disease-relevant cells, including cancer cells. The development of chromatin immunoprecipitation (ChIP)-based technologies, such as ChIP-chip and ChIP-Seq, has facilitated the high-throughput genome-wide mapping of epigenetic modifications that enable researchers to define the epigenome in disease-relevant cells and use comparative ChIP-based epigenetic mapping to correlate changes in epigenetic modifications with key physiological changes in disease-relevant tissues, including cancer cells, stem cells and T-cells. This feature review article provides insight into the nature of epigenetic modifications, the ChIP-based technologies that are available, and how such methods are being used to identify key epigenetic regulatory activities in medically relevant areas such as cancer and immunology.