Some observational studies and literature reviews suggest that antipsychotic drug use is associated with loss of grey or white matter in patients with schizophrenia, whereas others have contradicted this finding. Here, I summarize and critique the available evidence and put it in the context of clinical practice. This narrative review pools evidence from observational and experimental studies in humans and animals on the relationship between antipsychotic medication use and brain structure and function in patients with schizophrenia. To summarize, the observational evidence in patients with schizophrenia and the experimental evidence in animals suggest that antipsychotic drugs can cause reductions in brain volume, but differ as to where those effects are manifest. The experimental evidence in patients is inconclusive. There is stronger and more consistent evidence that other factors, such as alcohol and cannabis use, are likely causes of progressive brain changes in schizophrenia. Overall, I argue the case against antipsychotics is not proven and the jury is out on any significance of putative antipsychotic-induced brain changes. Taken in the context of strong evidence from clinical trials that antipsychotic drugs have beneficial effects on symptoms, function, relapse and cognition, and observational evidence that treatment normalizes other imaging indices and reduces mortality, the balance of probabilities is that antipsychotic drugs do not cause adverse structural brain changes in schizophrenia.