Pharmacogenetics provides great opportunity for improving both the chance of therapeutic benefit and the ability to avoid adverse drug events. To date, the majority of pharmacogenetic studies have been performed using germline DNA. DNA collection in most clinical trials provides a wealth of samples from which pharmacogenetic studies can be launched. However, there is concern that the data from germline DNA pharmacogenetics might be of limited value for diseases, such as cancer, where germline variants may not adequately represent the genetic data obtained from the somatic DNA. In this perspective, we evaluate the literature that compares pharmacogenetic variants between germline DNA and matched somatic DNA. The analysis of these studies indicates that there is almost complete concordance between germline and somatic DNA in variants of pharmacogenetic genes. Although somatic variants are clinically significant and independently provide genetic information that cannot be gained from the germline, the use of germline DNA for pharmacogenetic studies is achievable and valuable. This use of germline DNA offers great opportunities for the implementation of individualized therapy.