Before genetic approaches were applied in experimental studies with human populations, they were used by animal and plant breeders to observe, and experimentally manipulate, the role of genes and environment on specific phenotypic or behavioral outcomes. For obvious ethical reasons, the same level of experimental control is not possible in human populations. Nonetheless, there are natural experimental designs in human populations that can serve as logical extensions of the rigorous quantitative genetic experimental designs used by animal and plant researchers. Applying concepts such as cross-fostering and common garden rearing approaches from the life science discipline, we describe human designs that can serve as naturalistic proxies for the controlled quantitative genetic experiments facilitated in life sciences research. We present the prevention relevance of three such human designs: (1) children adopted at birth by parents to whom they are not genetically related (common garden approach); (2) sibling designs where one sibling is reared from birth with an unrelated adoptive family and the other sibling is reared from birth by the biological mother of the sibling pair (cross-fostering approach); and (3) in vitro fertilization designs, including egg donation, sperm donation, embryo donation, and surrogacy (prenatal cross-fostering approach). Each of these designs allows for differentiation of the effects of the prenatal and/or postnatal rearing environment from effects of genes shared between parent and child in naturalistic ways that can inform prevention efforts. Example findings from each design type are provided and conclusions drawn about the relevance of naturalistic genetic designs to prevention science.