Accurately identifying the cause of one's pain, discomfort, inflammation or other related musculoskeletal symptom(s) using current clinical imaging approaches, such as magnetic resonance imaging (MRI), computed tomography, digital radiography and ultrasound, is quite limited, lacks sensitivity/specificity and can even misguide treatment. As a musculoskeletal radiologist, I witness these shortcomings on a daily basis. Accordingly, our group has been developing clinical imaging methods that exactly pinpoint the site of pain generation using positron-emission tomography (PET) agents that specifically target molecular and cellular pain biomarkers to pinpoint 'painful' pro-inflammatory and/or pro-nociceptive tissues. Successful validation of this approach will aid in the objective diagnosis of pain generators and promote improved outcomes in those suffering with pain. This method also has the potential to facilitate more intelligent management of chronic pain, minimize unnecessary surgeries/opioid abuse, aid in the development of novel analgesics and potentially reduce the tremendous healthcare costs associated with the management of chronic pain. We are currently in clinical trials using PET/MRI and are realizing encouraging results in those suffering from chronic pain.