Image-guided interventional musculoskeletal procedures play a well-established role in diagnosis and therapy in modern medicine. Since these procedures are minimally invasive, a multitude of solid organ biopsies, fluid drainages, soft tissue injections, and joint injections can be performed with low complication rates. In this chapter, we describe percutaneous image-guided musculoskeletal biopsy, which include bony and soft tissue lesions, facet joint injections, and percutaneous vertebral augmentation.