Background: Removal of hardware with irrigation and debridement in patients with surgical site infections (SSIs) is performed commonly. However, the removal of hardware from patients with SSIs after spinal procedures is controversial. Moreover, primary spinal infections such as spondylodiscitis may require instrumentation along with surgical debridement. The purpose of this article was to evaluate critically and summarize the available evidence related to retention of hardware in patients with deep SSIs, and the use of instrumentation in surgical treatment of primary spinal infections. Methods: A literature search utilizing PubMed database was performed. Studies reporting the management of deep SSIs after instrumented spinal procedures, and of primary spinal infections using instrumentation published in peer-reviewed journals were included. Identified publications were evaluated for relevance, and data were extracted from the studies deemed relevant. Results: Because SSIs occur typically during the early post-operative period before stable bony fusion has been achieved, the removal of instrumentation may be associated with instability of the spinal column, pseudarthrosis, progressive deformity, pain, loss of function, and deterioration in the activities of daily living (ADL). Hence, early SSIs after spinal instrumentation are usually treated without removal of hardware. Moreover, primary spinal infections such as spondylodiscitis may require surgical debridement and instrumentation in cases with associated instability. Conclusions: Retaining or using instrumentation in patients with SSIs after spinal procedures or in patients with primary spinal infections, respectively, are commonly practiced in the field of spine surgery. Further evidence is required for the development of definitive algorithms to guide spine surgeons in decision making regarding the fate of instrumentation in the treatment of spinal infections.