Over the past two decades, the development of neuroimaging techniques has allowed the non-invasive investigation of neuroplastic changes associated with psychotherapeutic treatment. The aim of the present article is to present a systematic and critical review of longitudinal studies addressing the impact of psychotherapy on the brain published to date. After summarizing the results reported in the literature for each psychiatric disorder separately (i.e. obsessive-compulsive disorder, panic disorder, unipolar major depressive disorder, posttraumatic stress disorder, specific phobia, schizophrenia), we discuss the results focusing on three questions of interest: (i) whether neurobiological changes which follow psychotherapy occur in regions that showed significant neurofunctional alteration pre-treatment; (ii) whether these neurobiological changes are similar, or different, to those observed following pharmacological treatment; and (iii) whether neurobiological changes could be used as an objective means of monitoring the progress and outcome of psychotherapy. The evidence reviewed indicates that (i) depending on the disorder under investigation, psychotherapy results in either a normalisation of abnormal patterns of activity, the recruitment of additional areas which did not show altered activation prior to treatment, or a combination of the two; (ii) the effects of psychotherapy on brain function are comparable to those of medication for some but not all disorders; and (iii) there is preliminary evidence that neurobiological changes are associated with the progress and outcome of psychotherapy. It is hoped that a better understanding of the impact of psychotherapy on brain function will eventually inform the development of new biologically informed treatments and allow clinicians to make more effective treatment decisions.