Critical limb ischemia (CLI) is an already significant and growing epidemiologic problem with substantial implications for patient mortality, quality of life, and healthcare costs. Considerable progress has been made in its treatment and prevention; however, poor outcomes, especially with regard to limb loss, warrant further development of treatment options. This article will examine new advances being made in the area of limb salvage for this morbid disease. Open surgical techniques and materials such as distal vein patches and heparin-bonded PTFE will be discussed. Additionally, new developments in endovascular therapies with particular regard to infrapopliteal interventions and drug-eluting stents will be reviewed. Beyond the simple techniques and materials, there is a growing movement in the world of vascular surgery to examine surgical and endovascular interventions with regard to angiosome-oriented revascularization of ulceration and gangrene. This paradigm has the potential to change prioritization and planning of both types of therapies as further research into this concept develops.