Background:The processed electroencephalogram (EEG) is a useful surrogate effect measure in estimating opioid potency and latency to peak effect. However, the relationship between EEG determined potency and clinical measures of potency is unclear. The aim of this study was to characterize the relationship between EEG potency and clinical therapeutic windows for fentanyl, alfentanil and sufentanil and then apply this relationship to the new opioid remifentanil.Methods:The fentanyl congener literature published since 1980 was reviewed in detail. Articles reporting EEG or clinically based concentration‐effect relationships were analyzed. The relationship between the EEG potency and clinical measures of potency was examined for consistency and proportionality for all the fentanyl congeners. A generalized ‘fingerprint’ of this relationship was established. This fingerprint was then used to predict clinical therapeutic windows for the new opioid remifentanil. These predicted concentrations were compared to those actually measured in clinical trials.Results:The processed EEG is a reproducible measure of profound opioid effect. Therapeutic windows of the fentanyl congeners estimated in clinical studies relate to the EEG measure of potency in a reproducible, proportional way; that is, clinically determined therapeutic concentration ranges for specific surgical stimuli or drug synergism are a relatively constant fraction of the plasma concentration required to produce 50% of the maximal EEG effect (EC50) for all the fentanyl congeners. The generalized model of this relationship between EEG potency and clinical measures of potency based on data for alfentanil accurately predicted the remifentanil therapeutic windows estimated in clinical studies.Conclusions:The processed EEG is a useful surrogate measure of opioid effect. In addition to estimating potency and latency to peak effect, the EEG surrogate can also be used to estimate the therapeutic concentrations required for a variety of surgical endpoints. Thus, a single combined pharmacokinetic–pharmacodynamic EEG modeling study can yield not only information about potency and latency to peak effect but can also be used to predict the clinical pharmacodynamics of a novel opioid (as was the case in the remifentanil development program). This information can be useful in guiding a novel opioid development program, improving the efficiency of the overall development process.