Chronic pain exerts a tremendous burden on individuals and societies. If one views chronic pain as a single disease entity, then it is the most common and costly medical condition. At present, medical professionals who treat patients in chronic pain are recommended to provide comprehensive and multidisciplinary treatments, which may include pharmacotherapy. Many providers use nonopioid medications to treat chronic pain; however, for some patients, opioid analgesics are the exclusive treatment of chronic pain. However, there is currently an epidemic of opioid use in the United States, and recent guidelines from the Centers for Disease Control (CDC) have recommended that the use of opioids for nonmalignant chronic pain be used only in certain circumstances. The goal of this review was to report the current body of evidence-based medicine gained from prospective, randomized-controlled, blinded studies on the use of nonopioid analgesics for the most common noncancer chronic pain conditions. A total of 9566 studies were obtained during literature searches, and 271 of these met inclusion for this review. Overall, while many nonopioid analgesics have been found to be effective in reducing pain for many chronic pain conditions, it is evident that the number of high-quality studies is lacking, and the effect sizes noted in many studies are not considered to be clinically significant despite statistical significance. More research is needed to determine effective and mechanism-based treatments for the chronic pain syndromes discussed in this review. Utilization of rigorous and homogeneous research methodology would likely allow for better consistency and reproducibility, which is of utmost importance in guiding evidence-based care.