Half of all patients with squamous cell carcinoma of the head and neck (SCCHN) present with locally advanced disease. Despite the development of new treatment strategies, mortality rates have only improved over the last decade by 2.6% per year, and prognosis remains poor. Combined modality therapy offers the potential for organ preservation, particularly for tumors arising in the larynx, hypopharynx and oropharynx. Organ preservation with concurrent chemoradiotherapy (CRT) was first established in laryngeal carcinoma. Recent results of the laryngeal study, RTOG 9111, indicate that even though larynx preservation is improved with CRT compared to induction chemotherapy followed by radiotherapy alone, laryngectomy-free survival is the same. Future attentions should be focused not only on improving treatment efficacy, but also on efforts to minimize the long term toxicities of therapy for SCCHN, particularly because long term toxicities not only diminish quality of life, but seem to impact on survival. In the future, targeted therapies may be incorporated into combined modality therapy for SCCHN, offering the chance to enhance the anticancer effects of treatment without increasing toxicity. Improvements in radiotherapy techniques may also move the field forward. Finally, there is renewed interest in the role of induction chemotherapy as part of a sequential treatment approach for advanced SCCHN. If the current generation of studies evaluating sequential therapy is favorable, future studies incorporating targeted therapies into this platform will offer further potential for advancing the treatment of SCCHN.