Pharmacogenomics studies the influence of genomics on drug response safety and efficacy. Although research in this field was initiated many years ago, few functional applications are currently in use at the clinic. MicroRNAs (miRNAs) are short noncoding RNAs that bind genes and silence their expression. MiRNAs are encoded by the genome and expressed in all animal cells. MiRNAs are predicted to target approximately half of all human genes, and as a result regulate many cellular processes. The current focus of pharmacogenomics is the identification of polymorphisms in candidate genes coding for drug-metabolizing enzymes, drug transporters and drug targets. Here we call for the evaluation of miRNAs as an additional regulatory layer affecting pharmacogenomics. To illustrate the potential of miRNAs for affecting drug response we performed in silico evaluation of miRNA binding regions in genes known to affect drug response. We suggest that miR-133 and miR-137 may affect VKORC1 expression while miR-22 may affect MTHFR expression. We propose that miRNAs play a central role as a novel regulatory layer affecting drug metabolism and drug targets, and thus should be taken into consideration when conducting pharmacogenomic studies.