Since the number of prescriptions for opioid medications have continued to rise, there have been questions about the safety of using opioids in pain management. Traditionally, opioid analgesics were reserved for a few select conditions, such as terminal illness and surgery, but currently opioids have been readily prescribed for multiple conditions. The objective of this manuscript is to clarify the current state of opioid use and to discuss alternative transdermal analgesic therapies in pain management. Transdermal compounded medications are patient-specific and customizable to include different types of drugs, in various dosage strengths, that are to be delivered simultaneously in one application. Due to the different origins and types of pain, treatments may be most beneficial with multiple classes of drugs with various mechanisms of action. In addition, combination drug therapy may include nontraditional pain management options, and has the ability to maximize therapeutic effects of medications through additive or synergistic properties, without increasing the dosage strengths of the drugs. Many of the challenges faced when using oral opioid therapy may be overcome by using transdermal drug delivery since this route of administration reduces adverse effects, increases patient compliance, and limits exposure to potentially abusive drugs. Although prescribing practices surrounding opioids remains to be a controversial topic, the use of compounded pain medications may help healthcare providers effectively treat their patients while avoiding the use of addictive drugs.