Chromatin immunoprecipitation (ChIP) is a powerful technique for obtaining in vivo data on protein-DNA binding, providing an invaluable tool for elucidating gene regulation at a molecular level. Combined with high-throughput methods such as microarrays (ChIP-array) and second generation sequencing (ChIP-seq), the technique is now commonly used for answering questions about protein binding on a genome-wide level. This review focuses on the use of microarrays and sequencing for ChIP studies, provides a critical comparison of the currently used platforms and an overview of the computational methods available, and offers recommendations for optimal use of the techniques in a research context.