Ultrasound fusion is an established technique that pairs real time B-scan ultrasound (US) with other forms of cross-sectional imaging, including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Each of these imaging modalities has distinct advantages. CT provides superior anatomic resolution, with improved imaging of bone and calcified structures; MRI has superior contrast resolution; and PET provides physiologic information, identifying processes that are metabolically active (i.e., tumor, inflammatory conditions). However, these modalities are static. A key highlight of ultrasound is its capability of dynamic, real-time scanning. The ability to pair CT, MRI or PET with ultrasound can have significant advantages, both in diagnostic evaluation and when performing difficult or challenging image-guided interventions. Percutaneous interventions using ultrasound fusion have been described in the abdominal imaging literature; however, there have been very few musculoskeletal applications detailed in the literature. The purpose of this article is to review the basic concepts of real-time ultrasound fusion, and to detail, through the use of multiple case examples, its potential use as a safe and effective method for performing image-guided musculoskeletal interventions.