Pharmacogenomics research is becoming more prevalent in both academia and the pharmaceutical industry. While some discoveries have been integrated into practice and are benefiting patient care, these successes have been limited given the vast amount of research undertaken. However, the advances in high-throughput genomic technologies, better study designs and improved understanding of complexity, means that pharmacogenomic determinants of drug response will continue to be identified. It is important to develop an understanding of the basis of pharmacogenomics in clinical teams to allow accurate interpretation of the findings, and facilitate their implementation into clinical care (if appropriate). This article explains the science behind pharmacogenomics, and describes some of the challenges that have been encountered in the field, with a specific focus on paediatrics.