The group of drugs we call antidepressants have been available for nearly 60 years and are the first available physical treatment for depression that became accepted by the public and clinicians alike. However in the last decade, associated with the rise of evidence-based medicine and a concern about the medicalisation of distress, there has been a questioning and re-evaluation of their efficacy and place in the treatment of depression. This has occurred against the backdrop of increasing distrust of 'Big Pharma' and emphasis on psychological treatment approaches. I will be addressing some of the main challenges that have been put forward questioning the usefulness of antidepressants, ranging from the denial that depression is a disorder that can be treated by physical means, to the argument that there is no pharmacological or empirical evidence for a clinically useful benefit over psychologically-mediated placebo effects. To do this I will touch on recent developments in the understanding of how antidepressants might directly inşuence the processing by the brain of emotional material, consider the evidence that direct pharmacological effects are necessary to maintain the therapeutic effects of antidepressants and review the empirical evidence for clinically important efficacy from treatment trials in depression. I will conclude that while antidepressants are certainly not a panacea, denying their place in treating depression is based on prejudice rather than objective appraisal of the evidence.