The current body of evidence from both preclinical and epidemiologic studies suggests that cumulative stress may play a role in carcinogenesis; however, few studies on human populations have examined allostatic load (AL) as it relates to cancer risk, progression, and mortality. In this commentary, we discuss the use and value of AL as a measure to assess exposure to stress for cancer epidemiologic studies, describe the existing evidence between AL and sources of cancer-related environmental stressors, and summarize the existing epidemiologic studies on AL and cancer risk, progression, and mortality. We also outline several knowledge gaps and what steps should be considered to advance research on the role of AL and cancer risk, progression, and mortality in human populations.