The growing availability and inexpensiveness, as well as the ability to safely access musculoskeletal structures, have substantially increased the role of computed tomography for guidance of percutaneous biopsies in comparison to other imaging modalities like ultrasound and conventional fluoroscopy. CT-guided percutaneous fine needle aspiration biopsy (= FNAB) and core needle biopsy (= CNB) may be performed in essentially every organ system, while overall complication rates are low. CT provides an excellent visualization of bone, with the exception of some bone marrow lesions only detectable in MR imaging. Due to precise lesion and access visualization, structures at risk such as major vessels, nerves, and visceral structures can be avoided, and the biopsy needle precisely positioned within the target lesion for histopathologic sampling. Success rates of an individual institution depend on the number of samples obtained, the size of the lesion, the organ in which the biopsy is performed, the experience of the local pathologist staff, the available imaging equipment, and—first and foremost—the skills of the operator.