There is an increasing population of immunocompromised patients with HIV, IV drug abuse, organ transplantation, and long-term steroid treatment developing spinal infections. Delayed diagnosis because of blunted host immune response and lack of outward signs and symptoms places the treating physician at a disadvantage in the treatment of this type of disease, which presents at a later stage of development. Immunocompromised patients are infected by a different group of pathogens than their healthier cohorts (e.g., Pseudomonas, gram-negative bacteria and fungal infections) because their host defenses are diminished. Osteomyelitis with or with out pyomyositis and epidural abscess may occur. The overriding symptom is back pain. Radiculopathy, myelopathy, and sensory loss may accompany local pain and tenderness. Plain film radiography, CT scan, MR image, and bone scan is invaluable in the diagnosis of these infections. The cornerstone of treatment is identification of the responsible pathogen, appropriate medical therapy, immobilization of the affected segment of the spine, and physical therapy to combat physical deconditioning. Psoas abscesses may require surgical debridement if they cannot be adequately drained by CT-guided percutaneous catheterization. Epidural abscesses with neurologic compromise require surgical drainage. Impingement of the spinal cord or cauda equina by collapsed osteomyelitic vertebral bodies requires surgical debridement by anterior vertebrectomy, with an autologous tricortical iliac crest strut and immobilization of the spine using external bracing or posterior instrumentation as dictated by the disease.