Regional anesthesia is an essential component of contemporary anesthetic practice, enabling site-specific blockade of neural transmission to provide surgical anesthesia, postoperative analgesia, or both. Peripheral nerve blocks (PNBs) have expanded in popularity owing to their ability to improve pain control, reduce perioperative opioid use, facilitate rehabilitation, and contribute to enhanced recovery pathways. Blocks can be broadly categorized as plexus or peripheral nerve–targeted techniques (e.g., brachial plexus or lumbosacral plexus) versus truncal and fascial plane blocks (e.g., transversus abdominis plane (TAP), rectus sheath, erector spinae plane (ESP), paravertebral, etc.). Their clinical applications vary: some provide complete surgical anesthesia, while others serve primarily as adjuncts for postoperative pain relief. This chapter reviews commonly performed PNBs, including interscalene, supraclavicular, infraclavicular, and axillary brachial plexus blocks; femoral and adductor canal blocks; popliteal sciatic blocks; and truncal techniques such as TAP, rectus sheath, ESP, and paravertebral blocks. Common indications, basics of patient selection considerations, choice of local anesthetic, and complications are discussed. Special attention is given to anticoagulation and bleeding risk, with emphasis on the most recent 2025 American Society of Regional Anesthesia and Pain Medicine guidelines, distinguishing high-risk deep non-compressible blocks from safer superficial, compressible sites. Additional topics include the Bier block (intravenous regional anesthesia), adjuncts to local anesthetics (dexamethasone, dexmedetomidine, epinephrine, and sodium bicarbonate), and the widespread use of ultrasound guidance, which improves block accuracy, reduces complications, and enhances overall safety and quality. For internists and perioperative physicians, familiarity with these techniques enhances understanding of anesthesiologists’ choices, clarifies postoperative analgesic strategies, and frames anticoagulation discussions. Ultimately, PNBs exemplify the principles of precision, safety, and multimodal care that underpin modern anesthesiology practice.