Our objective is to provide a current perspective on the avoidable causes of global and US cancer incidence and mortality. Cancer registry-based incidence patterns, population behavioral risk-factor survey data, and systematic reviews of epidemiologic studies are the basis for estimates of relative risk, the prevalence of exposures to various lifestyle and environmental risk factors, and their impact expressed as population attributable fractions (PAFs). Of the total 59 million global deaths in 2008, 12-13% were attributed to cancer. The increasing burden of cancers in low- and middle-income countries (LMICs) is attributable in part to increasing urbanization, expansion of the adult population at risk, and increasing or persistent exposures to infectious agents, tobacco, and dietary deficiencies. Attributable fractions for lifestyle and environmental risk factors are summarized for the United States, the United Kingdom, and France. Assuming minimal overlap in the distribution of risk factors in the population and discounting the potential for interaction in their combined effects, we estimate that a maximum of 60% of cancer deaths in the United States may be attributed to eight risk factors: tobacco, alcohol, ionizing and solar radiations, occupations, infectious agents, obesity, and physical inactivity.