The causal pathways leading to depression involve a combination of genetic and environmental risk factors and the relative contribution of these factors differ across patients. In addition, patients vary in the way they respond to treatment. The aim of this article is to discuss a candidate gene approach (5‐HTTLPR) in the treatment of depression and how it may be implemented to individualize treatment plans for patients. First, we examine the role of 5‐HTTLPR polymorphisms in biased emotion processing and in the interplay between emotion regulation and cognitive control. An intriguing finding is that the low expression short allele variant of 5‐HTTLPR is best conceived as a gene that affects malleability or plasticity rather than specific vulnerability to depression. A shift from vulnerability to susceptibility has the potential to translate into new perspectives on individualized treatment of depression. The interplay between therapeutic intervention and genotype is a special case of gene‐environment interactions (GxE). Within this new field, recently named “therapygenetics,” a small number of studies have so far provided preliminary but provocative evidence of an association between the low expression 5‐HTTLPT short allele and response to psychological treatment. Future research should expand into randomized controlled trial (RCT) designs to examine the likelihood of response to psychotherapy versus pharmacotherapy in the individual patient.