Regulatory elements play an important role in the variability of individual 
responses to drug treatment. This has been established through studies on three 
classes of elements that regulate RNA and protein abundance: promoters, 
enhancers and microRNAs. Each of these elements, and genetic variants within 
them, are being characterized at an exponential pace by next-generation 
sequencing (NGS) technologies. In this review, we outline examples of how each 
class of element affects drug response via regulation of drug targets, 
transporters and enzymes. We also discuss the impact of NGS technologies such as 
chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing 
(RNA-Seq), and the ramifications of new techniques such as high-throughput 
chromosome capture (Hi-C), chromatin interaction analysis by paired-end tag 
sequencing (ChIA-PET) and massively parallel reporter assays (MPRA). NGS 
approaches are generating data faster than they can be analyzed, and new methods 
will be required to prioritize laboratory results before they are ready for the 
clinic. However, there is no doubt that these approaches will bring about a 
systems-level understanding of the interplay between genetic variants and drug 
response. An understanding of the importance of regulatory variants in 
pharmacogenomics will facilitate the identification of responders versus 
non-responders, the prevention of adverse effects and the optimization of 
therapies for individual patients.