The term opioid refers to a broad class of medications that are used most frequently for their analgesic effects. Along with this effect, they also produce euphoria, and it is for this reason that they have been used illicitly, as well as medicinally, for thousands of years. While the most well-known complications of opioid use and misuse include respiratory and central nervous system depression, there are many other toxicities that have been associated with these drugs. Many complications can occur with multiple different opioids, such as non-cardiogenic pulmonary edema, while many of the complications are unique to the opioid used as well as the route of administration. This review focuses on the pulmonary complications associated with opioid use and abuse, but opioids can affect nearly every organ system. Their effects on the pulmonary system can be direct, such as causing granulomatous change, but they can also work indirectly. For example, opioids cause respiratory depression by decreasing sensitivity of peripheral chemoreceptors to carbon dioxide and decreasing activity in the central respiratory centers. Opioids have also been reported to affect the immune system, and place users at increased risk for many different infectious complications. Patients can have a wide array of signs and symptoms, sometimes making it difficult to recognize opioids as a cause for a patient's clinical picture. Due to the sedative effects of opioids, patients are also often not able to provide a reliable history. Knowledge of the possible toxicities of opioids can help prepare a physician to recognize the many complications associated with opioid use.