For antidepressants as well as for other drugs, personalized prescription has become a major challenge, provided the large interindividual variability encountered both at the pharmacokinetic and the efficacy and tolerance levels. Better identification of the numerous relevant factors and quantification of their effects are prerequisites to progress in that direction. On the basis of recent literature, genetic factors are first reviewed, including polymorphisms of genes coding for drug-metabolizing enzymes, transporters and pharmacodynamic target molecules. Current recommendations with respect to therapeutic drug monitoring of antidepressants and use of pharmacogenetic testing are then summarized.