The rich, multidisciplinary history of cancer prevention recounted here begins with surgical and workplace recommendations of the 1700s and ends with 2009 results of the enormous (35,535 men) Selenium and Vitamin E [prostate] Cancer Prevention Trial (SELECT). This history comprises a fascinating array of chemopreventive, vaccine, surgical, and behavioral science research, both preclinical and clinical. Preclinical milestones of cancer prevention include the 1913 and 1916 mouse studies by Lathrop and Loeb of cancer development associated with pregnancy or cancer prevention through castration (oophorectomy), preventing chemically induced mouse carcinogenesis as early as 1929, energy restriction studies in the 1940s, the 1950s discoveries and later molecular characterizations of field cancerization and multistep carcinogenesis, and the effects of angiogenesis inhibition in genetically engineered mice reported in 2009. The extraordinary panoply of clinical research includes numerous large and smaller chemoprevention studies of nutritional supplements, other dietary approaches, a Bacillus Calmette-Guérin trial in 1976, molecular-targeted agents, and agents to prevent infection-related cancers such as hepatitis B virus vaccine to prevent liver cancer in 1984. Clinical surgical prevention includes removal of intraepithelial neoplasia detected by screening (including Pap testing developed in 1929 and culposcopy for cervical premalignancy and colonoscopy and polypectomy to prevent colorectal cancer begun in the 1960s) and prophylactic surgeries, such as in Lynch syndrome patients begun in 1977. Behavioral studies include smoking cessation and control beginning in the 1950s, obesity control rooted in studies of 1841, and genetic-counseling and cancer-survivorship studies. This history of pioneering events may help in better understanding who we are and what we want to achieve as cancer prevention researchers and practitioners.