Drug resistance is a major challenge in the treatment of epilepsy. Drug-resistant epilepsy (DRE) accounts for 30% of all cases of epilepsy and is a matter of great concern because of its uncontrollability and the high burden, mortality rate, and degree of damage. At present, considerable research has focused on the development of predictors to aid in the early identification of DRE in an effort to promote prompt initiation of individualized treatment. While multiple predictors and risk factors have been identified, there are currently no standard predictors that can be used to guide the clinical management of DRE. In this review, we discuss several potential predictors of DRE and related factors that may become predictors in the future and perform evidence rating analysis to identify reliable potential predictors. Display omitted •Overcoming drug resistance is a key challenge in epilepsy treatment.•Clinical and biochemical predictors can identify drug-resistant epilepsy (DRE).•Reliable predictors of DRE were obtained by evidence rating analysis.