Clinicians frequently use a crossover approach in switching antipsychotics, although historically there has been a lack of data addressing the question of switch strategies. To establish if there is now empiric evidence that may guide clinicians in this regard, a MEDLINE search to April 2004 was carried out to identify published, randomized and controlled trials that have addressed this topic. A total of 404 articles were identified in the search, which resulted in the identification of four reports meeting the criteria. The four studies evaluated switching strategies to one of three atypical antipsychotics: aripiprazole, olanzapine (two reports), and ziprasidone. The switching process itself could be subdivided as follows: discontinuation (abrupt vs. gradual); and, replacement (abrupt vs. gradual). Meta-analyses confirmed a lack of difference in outcome, regardless of approach. While a crossover approach does not appear to increase adverse events, the available empiric evidence does not support its clinical superiority on various outcome measures. The existing data therefore argue against the position that a crossover approach in switching antipsychotics represents a 'safer' means of preventing clinical deterioration during the switch.