Genetic analysis is slowly becoming a routine part of an individual's medical evaluation, not only in the selection and modification of therapies, but also the prediction and monitoring of a disease. In this study, pharmacogenomics and therapeutic drug management (TDM) were used to evaluate the clinical efficacy of genotyping chronic pain patients on analgesic therapy since the majority of therapeutic drugs prescribed for pain management are metabolized by polymorphic enzymes (e.g. cytochrome P450 2D6 (CYP2D6)). It was hypothesized that poor and intermediate metabolizers would have higher steady state concentrations of the drugs and be more likely to experience adverse drug reactions (ADRs). Prior to initiation of the study, IRB approval and witnessed, informed consent was obtained. DNA was extracted from whole blood using a Puregene^® DNA isolation kit. CYP2D6 genotyping (*3, 4, 5, 6, 7, 8, and gene duplication) were done using Pyrosequencing^®. Clinical evaluation of the patients included a detailed history and physical examination with emphasis on neurological, cognitive, and functional assessment. The steady-state plasma concentrations of methadone, oxycodone, hydrocodone, and tramadol were determined by LC/MS/MS. The results showed that the majority of the pain management patients (54%) were extensive metabolizers (EM), 41% were intermediate metabolizers (IM), and 5% were poor metabolizers (PM). In general, PM had the highest steady-state drug concentrations (Css) compared to EM (PM > IM > EM). In addition, a relationship between oxycodone Css and pain relief was found. Furthermore, 80% of all the individuals that reported ADRs also had impaired CYP2D6 metabolism. Overall, these results suggest that genotyping chronic pain patients along with TDM may lead to increased therapeutic efficiency and improve patient outcomes by minimizing ADRs. Future prospective studies are now needed to confirm the clinical utility of using genetic information to guide pain management therapy.