In addition to the genome and transcriptome, epigenetic information is essential to understand biological processes and their regulation, and their misregulation underlying disease. Traditionally, epigenetic DNA modifications are detected using upfront sample preparation steps such as bisulfite conversion, followed by sequencing. Bisulfite sequencing has provided a wealth of knowledge about human epigenetics, however it does not access the entire genome due to limitations in read length and GC- bias of the sequencing technologies used. In contrast, Single Molecule, Real-Time (SMRT) DNA Sequencing is unique in that it can detect DNA base modifications as part of the sequencing process. It can thereby leverage the long read lengths and lack of GC bias for more comprehensive views of the human epigenome. I will highlight several examples of this capability towards the generation of new biological insights, including the resolution of methylation states in repetitive and GC-rich regions of the genome, and large-scale changes in the methylation status across a cancer genome as a function of drug sensitivity.