Variation exists in patient response on analgesic treatment in terms of efficacy and safety. This variation may be in part explained by pharmacogenomics. This paper aimed to review data on pharmacogenomics of opioid analgesics focusing on the effect of genetic variation on the efficacy and safety of these agents. Current evidence suggests that pharmacogenomics contribute to variation in efficacy and safety of opioids. However, most data come from case control studies and case reports. In addition, a recognized drawback in the field of pharmacogenomics is the common occurrence of false positive association between polymorphisms and the investigated outcome. Prospective studies are needed to further elucidate the clinical implications of available data as well as to define the guidelines for the clinical application of pharmacogenomic data. Furthermore, basic research should focus on the identification of biologically meaningful polymorphisms enabling a hypothesis with biological plausibility driven research in the field of pharmacogenomics of analgesics. Moreover, the publication of relevant negative results should be favoured.