Genetic epidemiology is a rapidly expanding research field, increasingly focusing on complex diseases such as diabetes, ischemic heart disease, asthma and cancer. Due to the multifactorial nature of common complex diseases, dissecting the genetic basis and understanding the role of genetic and environmental factors of disease occurrence in the population require not only the application of both linkage and association analysis, but also the adoption of well planned and adequately powered study designs with an appropriate population base. The central concepts in modern genetic epidemiology are reviewed and illustrated using the example of breast cancer. The breast cancer susceptibility genes BRCA1 and BRCA2, which are associated with high disease risk, were initially identified by linkage analysis in families with multiple affected members. Risk assessment for mutation carriers based on molecular genetic mutation screening is nevertheless not straightforward because cancer risks have been found to vary substantially depending on the population studied, the extent of family history and birth cohort. Estimates of breast cancer risk are higher in BRCA1/2 mutation carriers from families with multiple affected members than from the population-based studies. Furthermore, the large variability in age at diagnosis is consistent with a modification of risk due to other genetic and environmental factors. Large international studies have provided the first evidence that risk factors for breast cancer in the general population may similarly affect breast cancer in BRCA1/2 mutation carriers, but this needs confirmation in prospective studies. Mutations in BRCA1 and BRCA2 account for less than 20% of the genetic risk of breast cancer so that much of the unexplained familial risk is likely to be due to low to moderate penetrance alleles. Association studies to date, which have focused on putative functional variants in genes that are candidates because of their known biological function, have yielded few definitive common susceptibility alleles. Adequately powered studies for genome-wide association studies to identify further susceptibility genes and genetic effect modifiers associated with moderate risk and replication studies with necessitate international collaboration. Clinical studies on preventive measures in mutation carriers have been conducted in Germany in 12 specialised centres within a conjoint project funded by the German Cancer Aid. Studies on novel preventive therapies are currently being carried out at the national and international level.