Response to pharmacotherapy can be highly variable amongst individuals. Pharmacogenomics may explain the interindividual variability in drug response due to genetic variation. However, besides genetics, many other factors can play a role in the response to pharmacotherapy, including disease severity, co-morbidity, environmental factors, therapy adherence and co-medication use. Better understanding of these factors and inter-relationships should bring about a much more effective approach to disease management. Systems biology that studies organisms as integrated and interacting networks of genes, proteins and biochemical reactions can contribute to this. Organisms are no longer studied part by part, but in a more integral manner. Integration of the genetic data with intermediate and end point phenotypic characterization may prove essential to define the inherent nature of drug effects. Therefore, in the future, a multidisciplinary systems-based approach will be necessary to deal with the bulk of the biological data that is available and, ultimately, to reach the goal of personalized prescribing.