More than 30 years ago, John Wolfe was the first to observe and describe the association between breast density on mammography and increased breast cancer risk. Following this pioneer work, there is now compelling evidence that density in the highest quartile represents a 4–6 times higher risk of breast cancer. This magnitude of risk is only topped by age and BRCA1/2 mutation. The density-based risk is independent of age and other risk factors. Apart from epidemiologic risk factors, additional genetic factors seem to influence density. This could be the reason behind the well-known interaction between genes and environment. Reliable and reproducible breast density measurements are a prerequisite for the use of breast density to monitor primary prevention strategies and for the use of mammographic density to define women at higher breast cancer risk who would benefit from intensified early detection and surveillance protocols.