The emerging field of proteomics offers great promise for unraveling the complex molecular events of tumorigenesis, as well as those that control clinically important tumor behaviors such as metastases, invasion, and resistance to therapy. Understanding the molecular basis of these tumor characteristics will usher in a new age of individualized cancer therapy. Advances in genomics, the study of genes and gene expression, as well as technologic advances have made possible study of all expressed proteins or the proteome (proteomics). Whereas genomics offers the opportunity to examine gene expression or variation in gene sequence, proteomics encompasses evaluation of protein expression, activation, modification, and degradation and ambitiously targets protein function. Although the present age has already been referred to as the post-genomic era, it is our opinion that both proteomics and genomics will provide clinically useful and complementary information that will speed scientific understanding of cancer. Ultimately, these new technologies will positively impact care of patients with head and neck squamous cell carcinoma.