Infections of the spine can be rapidly progressive and often cause significant neurologic deficits and even death. Unfortunately, they are also often difficult to diagnose, as they can mimic a number of other conditions. With rising numbers of patients who are immunosuppressed due to HIV, diabetes mellitus, and organ transplantation, these infections are becoming increasingly prevalent. Thus, it is important to know how to efficiently diagnose and initiate treatment for these patients. This chapter discusses the three main types of primary spinal infections: vertebral osteomyelitis, diskitis, and epidural abscesses. Also, atypical spinal infections are briefly discussed. While spinal infections can occur as a result of invasive procedures, this chapter will not include iatrogenic infections.