In recent years the discovery o f cancer biomarkers has become a major focus o f cancer research, which holds promise for early tumor detection and diagnosis and disease recurrence moni­toring and therapeutic efficacy. Proteomics technologies are emerging as a useful tool in the discovery o f cancer biomarkers: Substantial technological advances in proteomics and related computational science have been made in the past few years. These advances overcome in part the complexity and heterogeneity o f the human proteome, permitting the quantitative analysis and identification o f protein changes associated with tumor development. With the advent o f new and improved proteomic technologies, it is possible to discover new biomarkers for the early detection and treatment o f cancer. This chapter covers a selection o f advances in the realm o f proteomics and the discovery o f cancer biomarkers in recent years. The challenges ahead and perspectives o f proteomics for biomarker identification are also addressed. With a wealth o f information that can be applied to a broad spectrum o f biomarker research projects, this chapter serves as a reference for scientists working in proteomics and cancer.