Treatment-resistant depression (TRD) is a serious public health problem in view not only of its high prevalence (40-50% of outpatient depression patients fail to respond satisfactorily to treatment with antidepressants in monotherapy, with the correct dose, regime and duration) but also of its social significance (high medical cost) and the individual suffering it causes (poor prognosis, chronicity, increased risk of suicide, etc.). There is currently a lack of consensus on the conceptualisation of TRD and on therapeuthic approaches to it. However, in cases of partial or non-responders to antidepressant treatment, various alternatives have been proposed: optimisation of antidepressant dosage, substitution by another antidepressant agent (switching), addition of another drug that is not an antidepressant (augmentation) or addition of another antidepressant, generally from different pharmacological families (combination). The combination strategy is an option being used more and more frequently at the clinical level, and tends to be effective in 50-60% of cases, though this varies according to the drug employed. This paper reviews the state of the evidence on this therapeutic strategy, focusing on the family of antidepressants known as selective noradrenaline reuptake inhibitors (NARIs), particularly reboxetine, one of the antidepressants most widely used in combination therapy for TRD in recent years. The results obtained in combination strategies with reboxetine –especially in conjunction with SSRIs– suggest that it is a potentially useful tool. Nevertheless, there is a need for controlled studies to confirm the appropriateness of this combination strategy, since up to now all the published studies have been of open design.