During the last decade, a number of studies have supported the hypothesis that there is an important genetic component to the observed interpatient variability in normal tissue toxicity after radiotherapy. This review summarizes the candidate gene association studies published so far on the risk of radiation-induced morbidity and highlights some recent successful whole-genome association studies showing feasibility in other research areas. Future genetic association studies are discussed in relation to methodological problems such as the characterization of clinical and biological phenotypes, genetic haplotypes, and handling of confounding factors. Finally, candidate gene studies elucidating the genetic component of radiation-induced morbidity and the functional consequences of single nucleotide polymorphisms by studying intermediate phenotypes will be discussed.