Microvascular reconstruction of head and neck defects can be extremely challenging in patients with a history of prior neck dissection and/or irradiation. We reviewed of 261 head and neck free flaps performed between 2004 and 2007 at a tertiary cancer center. One hundred twenty-four (52%) free flaps were performed in patients with a history of prior neck dissection and/or irradiation. The ipsilateral external carotid artery or one of its branches was not available in 43 (19%) cases: 13 with no history of prior neck dissection or irradiation, and 30 with a history of prior neck dissection and/or irradiation (P = 0.03). The ipsilateral internal/external jugular veins (IJ/EJ) were not available in 37 (16%) cases: 11 with no history of prior neck dissection or irradiation, and 26 with a history of prior neck dissection and/or irradiation (P = 0.002). Strategies for dealing with lack of a recipient vessels included anastomosis to contralateral neck vessels, transverse cervical vessels, internal mammary vessels, the cephalic vein, and the pedicle of another free flap. We propose an algorithm for locating recipient vessels adequate for microvascular anastomosis should the ipsilateral external carotid arterial and/or the internal/external jugular venous systems not be available, such as in the setting of prior neck dissection or irradiation.