Objective In situ fenestration of endovascular stent grafts has been used as a method for branch vessel revascularization in urgent and emergent settings. The objective of this manuscript was to review the clinical and experimental evidence related to this technique. Methods PubMed, MEDLINE, and Embase databases were searched for papers published until December 2015 describing in situ fenestration of aortic stent grafts. Benchtop, animal, and human studies were included. Results The literature review identified 118 articles, of which 28 studies were selected for inclusion. These included 16 clinical papers (2 case series and 14 case reports) reporting in situ fenestration of 46 aortic branch vessels in 44 patients. There were 42 retrograde and 4 antegrade instances of in situ fenestration. The most frequent target vessel for in situ fenestration was the left subclavian artery (72%), and the most frequent indication for stent graft implantation was a degenerative aortic aneurysm (43%). Technical success was reported in 44 of 46 attempted fenestrations (96%). The combined rate of perioperative mortality, stroke, and paralysis was 7%. In situ fenestration was predominantly performed with the Talent (Medtronic, Santa Rosa, Calif) stent graft (54%), followed by the Zenith (Cook Medical, Bloomington, Ind) stent graft (37%) and the TAG (W. L. Gore & Associates, Newark, Del) stent graft (9%). In vitro benchtop evaluations of in situ fenestration showed minimal change in fenestration size after 1 year of pulsatile fatigue testing. The use of energy-based fenestration techniques (radiofrequency or laser) has been associated with less fabric fraying than in needle-based techniques. The larger caliber initial fenestration created by these devices also avoids the need for cutting balloons, which have also been linked with increased fabric tears and fraying of the fibers surrounding the fenestration. In addition, the Zenith stent graft was shown in benchtop testing to be the strongest in postfenestration mechanical testing, but it was also the most resistant to balloon dilation. Conclusions In the short to moderate term, in situ fenestration appears to be a reasonable and effective method to extend the proximal landing zone for revascularization of the left subclavian artery. However, longer follow-up is needed to fully assess the long-term durability of this procedure. Based on studies of material properties, an energy-based fenestration technique (radiofrequency or laser) is recommended, along with the avoidance of cutting balloons for dilation of the fenestration.