Ventral hernias represent the most common complication after abdominal surgery. Loss of domain and/or large ventral hernias in patients are especially challenging for surgeons to manage, but preoperative image-guided botulinum toxin injection has emerged as an effective adjunct to abdominal wall surgery. Loss of domain is caused by chronic muscle retraction of the lateral abdominal wall and leads to an irreducible protrusion of abdominal viscera into the hernia sac. Botulinum toxin can be used in the oblique muscles as a chemical component relaxation technique to aid abdominal wall reconstruction. Intramuscular botulinum toxin injection causes functional denervation by blocking neurotransmitter acetylcholine release resulting in flaccid paralysis and elongation of lateral abdominal wall muscles, increasing the rate of fascial closure during abdominal wall reconstruction, and decreasing recurrence rates. In total, 200-300 units of onabotulinumtoxinA (Botox®) or 500 units of abobotulinumtoxinA (Dypsort®) in a 2:1 dilution with normal saline is most commonly used. Botulinum toxin can be injected with ultrasonographic, EMG, or CT guidance. Injection should be performed at least 2 weeks prior to abdominal wall reconstruction, for maximal effect during surgery. At minimum, botulinum toxin should be injected into the external and internal oblique muscles at three separate sites bilaterally for a total of six injections. Although botulinum toxin use for abdominal wall reconstruction is currently not indicated by the Food and Drug Administration, it is safe with only minor complications reported in literature.