Opioids are frequently avoided as viable tools in the management of pain due to perceived dangerous or untoward adverse drug events. Whilst they are relatively safe options for the treatment of pain, side effects and toxicities do exist and should be anticipated by the provider. The central nervous, gastrointestinal, genito-urinary, integumentary, metabolic/endocrine, cardiovascular, pulmonary, hepatic/renal, ocular and immune systems all manifest changes associated with opioid therapy. These adverse events, ranging from nuisance to therapy-limiting, are manageable when addressed quickly and appropriately. Opioids are safe and efficacious analgesics when these effects are considered.