The edgeR package, an R-based tool within the Bioconductor project, offers a flexible statistical framework for detection of changes in abundance based on counts. In this chapter, we illustrate the use of edgeR on a human embryonic stem cell dataset, in particular for RNA-seq and ChIP-seq data. We focus on a step-by-step statistical analysis of differential expression, going from raw data to a list of putative differentially expressed genes and give examples of integrative analysis using the ChIP-seq data. We emphasize data quality spot checks and the use of positive controls throughout the process and give practical recommendations for reproducible research.