One of the major challenges in the head and neck oncology clinic is the need to identify biomarkers and/or gene expression signatures that complement, strengthen and increase the sensitivity and specificity of the current clinicopathologic analyses. Microarray analysis of head and neck tumors has demonstrated that the combined influence of many genes or biomarkers can make superior identifiers and/or predictors of tumor behavior and patient outcome. Here, an update of the recent literature on the prognostic and predictive value of microarrays for patients with head and neck squamous cell carcinomas is presented. Microarray technology has the potential for improved decision-making and corroboration within the clinical setting. However, further integration, standardization, validation and research are required before the use of microarray analysis is ready for routine clinical management of head and neck squamous cell carcinomas.