Metastasis to regional lymph nodes constitutes the main route toward progression and dissemination of head and neck carcinoma; at the same time it is the most significant adverse prognostic indicator for this disease. In recent years, significant focus has been given on the molecular mechanisms behind lymph node metastasis of head and neck cancer. The aim of this study is to assess the role of growth factor expression and function in association with lymph node metastasis and overall prognosis of head and neck cancer. Current literature, searching for experimental data regarding the molecular pathways of lymph node dissemination of head and neck cancer, is reviewed giving special emphasis on the expression and prognostic significance of specific growth factors. Members of the vascular endothelial growth factor (VEGF), mostly VEGF-C and VEGF-D, with their action through the receptors VEGFR-3 and VEGFR-2, constitute the most extensively studied growth factors associated with lymphangiogenesis so far. High expression of these as well as other molecules, including angiopoietins, insulin-like growth factor, and fibroblast growth factor, has been associated with lymph node metastasis and poor prognosis in head and neck squamous cell carcinoma. Numerous growth factors seem to play an important role regarding the lymph node metastatic potential of head and neck cancer. Further research is necessary in order to further clarify the molecular pathways and introduce novel therapeutic options.