It is now well established that the interplay of sequence-specific DNA binding proteins with chromatin components and the subsequent expression of differential genetic programs is the major determinant of developmental decisions. The last years have seen an explosion of basic research that has significantly enhanced our understanding of the basic principles of gene expression control. While many questions are still open, we are now at the stage where we can exploit this knowledge to address questions of how deregulated gene expression and aberrant chromatin programming contributes to disease processes. This chapter will give a basic introduction into the principles of epigenetics and the determinants of chromatin structure and will discuss the molecular mechanisms of aberrant gene regulation in blood cell diseases, such as inflammation and leukemia.