Musculoskeletal (MSK) disorders are associated with large impacts on patient's pain and quality of life. Conventional morphological imaging of tissue structure is limited in its ability to detect pain generators, early MSK disease, and rapidly assess treatment efficacy. Positron emission tomography (PET), which offers unique capabilities to evaluate molecular and metabolic processes, can provide novel information about early pathophysiologic changes that occur before structural or even microstructural changes can be detected. This sensitivity not only makes it a powerful tool for detection and characterization of disease, but also a tool able to rapidly assess the efficacy of therapies. These benefits have garnered more attention to PET imaging of MSK disorders in recent years. In this narrative review, we discuss several applications of multimodal PET imaging in non-oncologic MSK diseases including arthritis, osteoporosis, and sources of pain and inflammation. We also describe technical considerations and recent advancements in technology and radiotracers as well as areas of emerging interest for future applications of multimodal PET imaging of MSK conditions. Overall, we present evidence that the incorporation of PET through multimodal imaging offers an exciting addition to the field of MSK radiology and will likely prove valuable in the transition to an era of precision medicine.