Epidemiologic evidence increasingly has supported the role of biobehavioral risk factors such as social adversity, depression, and stress in cancer progression. This review describes in vitro, in vivo, and clinical studies demonstrating relationships between such processes and pathways involved in cancer progression. These include effects on the cellular immune response, angiogenesis, invasion, anoikis, and inflammation. Biobehavioral factors have been shown to contribute to the cross talk between tumor and host cells in the tumor microenvironment, and stress effects on host cells such as macrophages seem to be critical for many pathways involved in tumor progression. Some effects are bidirectional in that tumor-derived inflammation seems to affect central nervous system processes, giving rise to vegetative symptoms and contributing to dysregulation of the hypothalamic-pituitary-adrenal axis with downstream effects on inflammatory control. Findings to date are reviewed, and fruitful areas for future research are discussed.