Inherited factors that increase cancer susceptibility can be due to mutations in rare, high-penetrance genes, less rare moderate susceptibility genes, or a combination of common genetic variants of small effect. These genes can be tumor suppressor genes (TSGs), DNA repair genes or oncogenes, and others such as those involved in the immune response or vascular growth promotion. Mutations in TSGs can cause conditions with a distinct phenotype such as familial adenomatous polyposis; DNA repair gene alterations can cause breast/ovarian cancer susceptibility and Lynch syndrome. The underlying causes of leukemia include rare mutations in highly penetrant genes but more commonly is multifactorial.The principles of genetic counseling are based on the knowledge of these genetic mechanisms, predicated on the facility for making a molecular diagnosis in an affected proband, which then allows cascade predictive testing in the at-risk relatives of cases. There are important issues of the ownership of genetic information and confidentiality, which need to be taken into account when delivering genetic counseling. Predictive tests can allow appropriate clinical risk-reducing management to be developed for tested individuals.