Case series outlining the treatment of three patients with ketamine, in which two of the patients had a sustained antidepressant effect to ketamine without the need for maintenance on antidepressants. These two responders have an established diagnosis of bipolar affective disorder with a history of response to electroconvulsive therapy and lithium, both of which have an influence on the seizure threshold as has ketamine. The mechanism of action of ketamine is yet unclear and although the current focus is on the N-methyl-d-aspartate and alpha-amino-3-4-hydroxy-5methyl-4-isoxazoleproprionic acid receptors, we additionally recommend that its impact on the seizure threshold should be explored with a view to fully elucidating the mechanism of action.