Methylation at the 5 position of cytosine is a form of covalent DNA modification found in a variety of species including plants and mammals. It plays an important role in gene regulation, chromatin structure, and a variety of other biological processes. It serves as an epigenetic mark and has been shown to change in response to environmental factors and disease. Owing to its importance in gene regulation, there has been considerable interest in trying to understand the role of DNA methylation in the production of organism-level phenotypes and especially in its contribution to human health and disease. Studies in many organisms have revealed large amounts of variation in DNA methylation between individuals. This interindividual variation in DNA methylation is highly complex. The amount of variation detected is locus- and tissue-specific and can be caused by genetic as well as environmental factors. In this chapter, we review the available data on interindividual variation in DNA methylation, its origins, and its consequences with a particular focus on its role in human disease.