Purpose of Review This study aimed to contribute to the debate on the availability of opioids for pain management by comparing regional and global trends for controlled strong opioids most commonly used for pain over the past 21 years. We conducted a series of analyses on the use of 12 opioids, with a focus on fentanyl, hydrocodone, hydromorphone, morphine, and oxycodone over the 21-year period of 1995–2015, at a regional and global level with country-level data, using random intercept mixed models to assess for change over time and interactions, and controlling for country economic development. Recent Findings Despite the sufficient supply of opioids to cover global demand, potent opioid pain medications are not available in many regions of the world. Prices of basic off-patent opioid formulations are significantly higher in poor countries as compared to lowest global prices, whilst countries may be under pressure to acquire expensive formulations. This results in lower availability of opioids for pain management in lower-income countries. Summary The analysis shows that, when adjusted for country-level gross domestic product (GDP) per capita and Human Development Index (HDI) category, the most significant trends in opioid consumption for pain management are those of morphine and fentanyl. Whilst the trend for use of morphine has remained relatively stable, fentanyl use has risen sharply in the past 21 years, even in regions where the levels of overall opioid availability are inadequate or very inadequate. The trends vary according to different regions of the world.