Increasing use of nitrous oxide as a recreational drug has been reported among young adults in western countries over the past decade. We present two cases of young males presenting to the Emergency Department (ED) of a large urban university hospital in Dublin with progressive neurological dysfunction related to nitrous oxide use. We review the pathophysiology, clinical features and treatment of nitrous oxide neurotoxicity. It is important that clinicians are aware of this evolving public health issue and are able to recognize the clinical features of this rare presentation, which may become more common in Irish EDs and GP surgeries as nitrous oxide abuse becomes more prevalent.