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Objectives This article reviews evidence regarding effects of psychotherapy on overall cancer survival time. Special emphasis is given to research on adverse effects of depression on cancer survival, breast cancer, and mediating psychophysiological pathways linking psychosocial support to longer survival. Design It reviews all published clinical trials addressing effects of psychotherapy on cancer survival, emphasizing depression, breast cancer, and psychophysiological evidence linking stress, depression, and support to cancer survival. Methods Systematic literature review and synthesis. Results Eight of 15 published trials indicate that psychotherapy enhances cancer survival time. No studies show an adverse effect of psychotherapy on cancer survival. Potential psychophysiological mechanisms linking stress to shorter survival include dysregulation of diurnal cortisol, increased pro-inflammatory cytokines, reduced natural killer cell activity, shorter telomeres and lower telomerase activity, glucocorticoid-mediated suppression of p53 and Br CA1 gene expression, and sympathetic nervous system activation of vascular endothelial growth factor. Conclusions Stress and support affect the course of cancer progression. Statement of contribution What is known? Stress and support have been thought to be related to cancer risk and progression, but evidence has been mixed., Depression is a natural co-morbid condition with cancer., It has not been clear how stress and support could physiologically affect the rate of cancer progression., Immune function was not thought to have much relevance to cancer progression., Few other physiological mechanisms linking stress to cancer progression were known., What does this paper add? There is evidence from 15 RCTs indicating that effective psychosocial support improves quantity as well as quality of life with cancer., There is evidence that chronic depression predicts poorer prognosis with cancer., Dysregulated circadian cortisol patterns predict more rapid cancer progression., Inflammatory processes affect cancer growth and progression., Sympathetic nervous system activity, telomere length, telomerase activity, and oncogene expression are affected by stress and can affect cancer growth. [ABSTRACT FROM AUTHOR]