DNA methylation is generally considered to be associated with transcriptional silencing. However, comprehensive, genome-wide investigation of this relationship requires the evaluation of potentially millions of correlation values between the methylation of individual genomic loci and expression of associated transcripts in a relatively large numbers of samples. Methodical makes this process quick and easy while keeping a low memory footprint. It also provides a novel method for identifying regions where a number of methylation sites are consistently strongly associated with transcriptional expression. In addition, Methodical enables housing DNA methylation data from diverse sources (e.g. WGBS, RRBS and methylation arrays) with a common framework, lifting over DNA methylation data between different genome builds and creating base-resolution plots of the association between DNA methylation and transcriptional activity at transcriptional start sites.