Although widely present in clinical guidelines as a way of identifying serious spinal pathology, there is a lack of evidence supporting the validity of multiple commonly listed red flags. Moreover, the presence of individual red flags seldom provides reliable information. The combined presence of red flags may provide more valuable information, but further studies are still necessary to confirm this. In order to accurately determine the level of suspicion of serious spinal pathology warranted in each case, clinicians should take into account both the evidence regarding red flags and each patient’s health determinants. This is concluded by an expert panel of the International Federation of Orthopaedic Manipulative Physical Therapists (IFOMPT) that has drawn up a framework on this specific matter.