Key points Chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) increased and prolonged the long‐term potentiation‐like plasticity induced by anodal transcranial direct current stimulation (tDCS) for over 24 h. Chronic administration of RBX converted cathodal tDCS‐induced long‐term depression‐like plasticity into facilitation for 120 min. Chronic noradrenergic activity enhancement on plasticity of the human brain might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases. Abstract Noradrenaline affects cognition and motor learning processes via its impact on long‐term potentiation (LTP) and depression (LTD). We aimed to explore the impact of single dose and chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) on plasticity induced by transcranial direct current stimulation (tDCS) in healthy humans via a double‐blinded, placebo‐controlled, randomized crossover study. Sixteen healthy volunteers received placebo or single dose RBX (8 mg) before anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took RBX (8 mg day−1) consecutively for 21 days. During this period, two additional interventions were performed (RBX with anodal or cathodal tDCS), to explore the impact of chronic RBX treatment on plasticity. Plasticity was monitored by motor‐evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic administration of RBX increased and prolonged the LTP‐like plasticity induced by anodal tDCS for over 24 h. Chronic RBX significantly converted cathodal tDCS‐induced LTD‐like plasticity into facilitation, as compared to the single dose condition, for 120 min after stimulation. The results show a prominent impact of chronic noradrenergic enhancement on plasticity of the human brain that might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases.