Nuclear medicine procedures are part of the evaluation armamentarium used in patients with suspected or confirmed infection. The strength of functional imaging modalities rests on their being non-invasive tests that provide pathophysiological information early in the course of disease. Their limitations, related to a somewhat low specificity of radiotracers and image resolution, have largely been overcome over the last 15 years following the introduction of the hybrid SPECT/CT technology. SPECT/CT is redefining the diagnostic workup of patients with suspected or known infectious and inflammatory processes involving the musculoskeletal system as well as those with infectious and inflammatory disease located in various soft-tissue sites. Furthermore, it has been shown that in addition to improving diagnostic accuracy (by adding specificity to the inherent high sensitivity of single-photon emission tomography), SPECT/CT leads to changes in the subsequent clinical management of patients. The main indications for SPECT/CT in infection, as well as updated literature data on this topic, are presented in the following review.