Blood flow restriction (BFR) therapy is an emerging clinical modality utilizing the metabolic stress of a hypoxic state to induce hypertrophic and strength adaptations in a manner allowing for reduced external loading. BFR has a variety of applications in rehabilitation settings, showing great potential for patients seeking the benefits of high intensity training without the associated degrees of mechanical stress. This literature review details the proposed mechanisms of BFR, along with various clinical applications of BFR including active and aerobic BFR. Concerns and contraindications for BFR usage are discussed regarding certain clinical populations, with risk stratification recommendations provided. Current BFR technology is considered, and clinical application guidelines are specified for safely inducing hypertrophic and aerobic benefits in clinical populations.