Rare, high-penetrance genetic variations account for a small portion of genetic cancer syndromes. In contrast, most cancers develop from a combination of minor genetic influences and environmental factors. There are numerous publications on cancer susceptibility. In contrast, genetic studies in treatment response and outcome analyses are a rapidly emerging field. Approaches used in disease susceptibility can be adapted for genetic outcome studies. In this review, we summarize the current knowledge on how candidate genes and genetic variations are selected to evaluate gene-outcome, gene-prognosis, and gene-treatment response relationships as applicable to the practicing oncologist.