Large interindividual variation in efficacy and adverse effects of anti-epileptic therapy presents opportunities and challenges in pharmacogenomics. Although the first true association of genetic polymorphism in drug-metabolizing enzymes with anti-epileptic drug dose was reported 10 years ago, most of the findings have had little impact on clinical practice so far. Most studies performed to date examined candidate genes and were focused on candidate gene selection. Genome-wide association and whole-genome sequencing technologies empower hypothesis-free comprehensive screening of genetic variation across the genome and now the main challenge remaining is to select and study clinically relevant phenotypes suitable for genetic studies. Here we review the current state of epilepsy pharmacogenetics focusing on phenotyping questions and discuss what characteristics we need to study to get answers.