This chapter provides detail about the acute lower extremity pain. The lower extremity is a common site for acute pain or chronic pain with acute exacerbations. The common etiologies include traumatic, degenerative, oncologic, infectious, ischemic, and neuropathic. Lower extremity pain may also be referred from intervertebral discs, facet joints, and sacroiliac joints. Successful treatment of acute lower extremity pain can be optimized utilizing a multimodal approach with medications, physical therapy, graded exercise, and interventional procedures such as regional anesthesia. In a nonsurgical patient, regional anesthesia may also be useful for helping to break the pain cycle. Pharmacologic treatment of acute lower extremity pain typically includes analgesic medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, anticonvulsants, antidepressants, and opioids. A well-illustrated table on methods for blocking nerves of the lower extremities has been also presented in this chapter.