DNA methylation is among a growing list of epigenetic modifications that have important roles in regulating gene expression and therefore is involved in a broad range of biological processes and diseases. Epigenetic profiles, including DNA methylation, are tissue-specific, contribute to cell identity, and can be dynamic during development. In this chapter, we discuss genome-wide and locus-specific techniques that divide into three main categories: restriction enzyme digestion, affinity-based analysis, and bisulfite modification. In general, candidate biomarkers are discovered using large-scale, genome-wide sequencing and/or microarray-based profiling strategies, with confirmation performed using various PCR-based methods. We also describe the emerging state-of-the-art technologies for single-cell epigenome profiling and the integration of various protocols for innovative multi-omic analyses that allow researchers to disentangle cell and tissue heterogeneity that is particularly relevant for reproductive epigenomics.