Here, we provide an overview of previous family studies of addiction and present a new family study based on clinical data for more than 19,000 individuals who have been treated for addiction in Iceland over the last three decades. Coupled with the extensive Icelandic genealogy information, this population-based sample provides a unique opportunity for family studies. The relative risk (RR) was determined for up to fifth-degree relatives of probands diagnosed with alcohol, cannabis, sedative, and amphetamine dependence. We observe highly significant RR values for all substances ranging from 2.27 for alcohol to 7.3 for amphetamine, for first-degree relatives, and RRs significantly above 1 for distant relations, where the effect of shared environmental factors is minimized. The magnitude of risk in psychostimulant dependence is particularly striking. These findings emphasize the role of genetics in the etiology of addiction and highlight the importance of substance-specific effects.