It is widely accepted that an individual's environment plays a significant role in the probability that they will develop breast cancer. Given the common nature of breast cancer, it is suspected that environmental risk factors will also be common; however, epidemiological evidence shows that individual response to environmental risk factors is highly variable. Common genetic factors are the most obvious source of this observed variation. An effective study design and statistical model for identifying common environmental and genetic interactions must have several characteristics. First, a population-based approach with a well-defined sampling scheme must be taken. Next, the assessment of environmental risk factors must be given serious consideration, with the complexity of the variables taken into account. Genetic variation must be quantified in a way that will maximize the amount of information while being statistically efficient. Most important, hypotheses should be designed, and statistical models constructed, to take into account what is known about the biology of breast cancer. I will describe the importance of these characteristics in detail, providing examples taken from the literature and my own past and ongoing research.