Understanding how antidepressant drugs exert their effects in the human brain remains a major challenge in neuropsychopharmacology. In this talk, I will present our recent efforts to translate key findings from preclinical animal models into human neurocognitive paradigms of antidepressant drug action including behavioural and imaging approaches. I will discuss work spanning both established antidepressant medications and fast-acting, next-generation treatments, including ketamine. By integrating animal and human approaches, this work aims to bridge mechanistic insights across species and improve the way in which treatments for depression are understood and developed.