Opioids can provide effective analgesia by way of different routes of administration without limiting side effects for most patients suffering from chronic pain when clinicians properly manage the pertinent patient-, pain-, and drug-centered characteristics. Randomized, placebo-controlled, prospective studies are needed to establish a causal relationship between opioids and hypogonadism. Many of the current studies are retrospective, which only lead to suggestive associations between opioids and hypogonadism and incorporate bias. Clinicians may incorporate available tools, including urine toxicology tests, to assess any aberrant behavior on the part of patients using opioids and to maximize compliance with an opioid regimen.