This article provides up-to-date information regarding clinical manifestations, pathophysiology, and evidence-based treatment for tardive dyskinesia (TD). We conducted a comprehensive literature search, including sources such as the Cochrane Library, EMBASE, and Medline; and we manually searched bibliographic references. We also contacted the authors of each included trial. All randomized clinical trials that compared different types of active interventions with placebo or no intervention in patients with neuroleptic-induced TD were included in our data. Two reviewers independently applied the selection criteria to all identified references, appraised the methodological quality of each trial, and extracted the relevant data. Relative risks and 95% confidence intervals were estimated using the fixed effect model. More than 500 randomized trials evaluating over 90 different interventions to treat TD were identified. From those, 45 trials were included in the current reviews. None of the trials pooled on these reviews found a definitive therapy for TD. Clinicians faced with conditions such as TD should carefully weigh the risks and benefits involved with any given intervention.