Post-operative Respiratory Depression (PORD) is a common and frequently serious complication of surgeries occurring in up to 20% or more of surgeries.  Post-operative pain management is still a significant problem with over 80% of patients having moderate to severe pain.  Opioids are still the mainstay of treatment for post-operative pain.  However, the use of opioids to treat post-operative pain has been a myopic focus, as far as etiology of PORD.  Multiple other factors play a role in PORD however; benzodiazepines, propofol, paralytic agents, gaseous anesthetics and other drugs have all been shown to impair respirations post operatively.  Frequently the current clinical approach is to use naloxone to reverse PORD.  However, polypharmacy is a clear contributor to PORD.  Naloxone certainly has a role, but will not reduce the respiratory depression caused by benzodiazepines, propofol and other respiratory depressants.  A different paradigm of PORD needs to be discussed and other contributors, other than just opioids, need to be taken into consideration.  This presentation will present the recent data on PORD and suggest new definitions as well as potential new therapies such as respiratory stimulants.