The autonomic nervous system is composed of the sympathetic and parasympathetic nervous systems. The sympathetic nervous system is implicated in situations involving emergent action by the body and additionally plays a role in mediating pain states and pathologies in the body. Painful conditions thought to have a sympathetically mediated component may respond to blockade of the corresponding sympathetic fibers. The paravertebral sympathetic chain has been targeted for various painful conditions. Although initially injected using landmark-based techniques, fluoroscopy and more recently ultrasound imaging have allowed greater visualization and facilitated injections of these structures. In addition to treating painful conditions, sympathetic blockade has been used to improve perfusion, treat angina, and even suppress posttraumatic stress disorder symptoms. This review explores the anatomy, sonoanatomy, and evidence supporting these injections and focuses on ultrasound-guided/assisted technique for the performance of these blocks.