Amputation of the lower limb is associated with high morbidity and mortality. Common indications of amputation include trauma, gangrene, tumor and infections. One needs to do meticulous perioperative care including monitoring to ensure low morbidity and mortality. Multimodal analgesia including pharmacological components like regional anesthesia, opioids, nonopioid systemic analgesics, nonsteroidal anti-inflammatory drugs, and various adjuvants. Regional anesthesia has been used effectively and shown to improve stump flow, provide postoperative analgesia, reduces postoperative pulmonary dysfunction, and decreases incidence of cognitive dysfunction. The nerve supply of the lower limbs is derived from the lumbar and sacral plexus. The regional blocks targeting these nerves can be used in combination for effective analgesia.