Currently, an increasing number of studies about systemic laser photobiomodulation (FBM), have been highlighted in the literature; however, they differ in their application methods, which can be intravenous (intravascular laser irradiation of blood), or transdermally, (vascular photobiomodulation). This review aimed to compile all findings on these techniques and critically discuss their results. A search for articles was conducted in the PubMed, Scopus, and Web of Science databases. After applying inclusion and exclusion criteria, 37 articles were selected. Of these, 19 studies discussed the use of systemic FBM with intravenous application, and 7 studies reported transcutaneous application. Regarding clinical studies, 28 studies addressed the application of the techniques in respiratory, cardiovascular, metabolic, neurological, and musculoskeletal conditions. For preclinical studies, 9 articles primarily discussed the application in pulmonary and musculoskeletal conditions. Despite the promising results, methodological limitations and variabilities in studies on systemic laser FBM prevent the categorical assertion of its efficacy.