Antidepressants, mainly tricyclic and non-selective reuptake inhibitors of serotonin antidepressants, are part of the treatment of chronic pain. The management is complicated by a large interindividual variability of efficacy and tolerance. Important part of this variability is associated with nucleotide polymorphisms of genes encoding enzymes involved in the pharmacokinetics and pharmacodynamics of these molecules. Identification of these genetic variants could to predict clinical consequences and allowed individualized adjustments in medication or dosage. This article presents the current knowledge on the influence of genetics on the efficacy and adverse effects of antidepressants used in chronic pain treatment.