Postoperative wound infection after spinal surgery remains a serious and common complication. Despite the development of prophylactic antibiotics and advances in the surgical technique and postoperative care, wound infection continues to compromise patient outcomes after spinal surgery. Given the wider application of spinal instrumentation in the recent years, the management of related postoperative infections has become increasingly important. Possible infectious complications comprise discitis, epidural abscess, meningitis, osteomyelitis, and superficial and deep wound infections. Deep wound infection is the most common infection encountered after the insertion of hardware to the spinal column. Currently with routine antibiotic prophylaxis before spine surgery, the incidence of infection after lumbar discectomy or laminectomy is approximately 1%. Recent estimates from retrospective reviews clearly indicate the increased risk for postoperative infections of soft tissue after spinal instrumentation and range from 2.1 to 8.5%. Though, the most appropriate method for managing wound infections in the presence of spinal instrumentation is controversial. The treatment varies in the literature with regard to superficial or deep infection; the use of drains, drainage systems and local antibiotic delivery devices; removal of hardware; and closure method. The present chapter reviews the literature on postoperative spinal wound infection in case of spinal instrumentation and their current treatment protocol.