The anterolateral thigh flap is a septocutaneous artery flap based on the septocutaneous or muscle perforators of the lateral circumflex femoral system. Little has been reported about the variations in its vascular anatomy and its application for head and neck reconstruction. We report 22 cases in which this flap was used for the reconstruction of head and neck defects. Based on our clinical and cadevaric experiences, the derivation of the vascular pedicle of this flap has four variations by which the septocutaneous perforators are derived from the descending branch of the lateral circumflex femoral system and/or from the transverse branch of that system, or for which there are no septocutaneous perforators but there are muscle perforators originating from the lateral circumflex femoral system. Clinically, the vascular variations and the locations of perforators of this system can be determined preoperatively with stereoangiograms or simple angiograms and Doppler audiometry. The anterolateral thigh fasciocutaneous flap is suitable for reconstruction of defects in an oral floor with tongue and esophageal deficits, scalp defects with dural defects, and for large full thickness defects of the lip. The advantages of this flap are safe elevation, a long and wide vascular pedicle, skin that is generally thin, and good pliability. Even if the skin is thick, a thinner flap can be created by sacrificing a large amount of fatty tissue. Furthermore, the skin territory is very wide and long. The donor defect can often be closed directly with its scar being less noticeable. The disadvantage of this flap is that the anatomy of the pedicle vessels has irregular derivation from the main vessels. This can be overcome, however, by employing preoperative stereoangiograms.