The administration of chemotherapy either alone or in combination with radiotherapy is an important factor in reducing the mortality and morbidity of cancer patients. Resistance to both chemotherapy and radiotherapy represents a major obstacle to a successful outcome. The identification of novel biomarkers that can be used to predict treatment response would allow therapy to be tailored on an individual patient basis. Although the mechanisms are unclear, it is accepted that development of therapy resistance is a multifactorial phenomenon involving alterations in several cellular pathways. Proteome analysis methods are powerful tools for identifying factors associated with resistance to anticancer therapy because they facilitate the simultaneous analysis of whole proteomes. The current review describes the plethora of existing proteomic approaches and details the studies that have identified biomarkers that may be useful in the prediction of clinical response to anticancer therapy. Cancer 2006. © 2006 American Cancer Society.