Head-neck cancer is an area requiring more attention to a highly demanding therapy which has not been fully developed yet. Despite advances in diagnosis and treatment, including improvements of surgical techniques, radio- and chemotherapy and prevention strategies, the survival rates of patients with recurrent head-neck cancer are low. New drugs, including those targeting the epidermal growth factor receptor, p53 gene, RAS protein post-translation modification, the proteosome, vascular endothelial growth factor, cyclooxigenase-2 and other molecular pathways, are promising agents for management of head-neck cancer. Their potential is being tested in various settings, including chemoprevention, recurrent and metastatic disease and combination with radiotherapy and/or cytotoxic agents. Cytotoxic drugs could produce better effects if administered locally--laser thermal cisplatin application. The metronomic low-dose chemotherapy will prove effective. The anticoagulant therapy undoubtedly has its place. The potential lies in sound ongoing academic clinical trial--biomarkers leading to maximally promising pharmacogenomic based therapy. Better comprehension of tumor biology and mechanisms of resistance is necessary as well as the institution of reliable assays for clinical use.