Cell-free DNA in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells, and retain some of the cell of origin histone modifications. In recent years my group developed chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) as a non-invasive diagnostic assay. This assay provides rich information about the transcriptional states of cells dying within the body. In this talk I will briefly describe the technology, the promise and challenges it presents, and its application in detecting and understanding human disease.