Tamoxifen (TAM) is a non-steroidal selective estrogen receptor modulator that was approved by the FDA in 1977 for the treatment of breast cancer. Although it is generally well tolerated, significant adverse effects have been reported, including severe hot flashes and an increased risk for venous thromboembolism and endometrial cancer. The phase I metabolism of TAM is primarily performed by CYP2D6 and CYP3A4/5, resulting in the major, active metabolites N-desmethyl-4-hydroxy-tamoxifen (endoxifen) and 4-hydroxy-tamoxifen (4-OH-TAM). Interestingly, CYP2D6 variant genotypes that result in an inactive or less active phenotype results in greater levels of circulating endoxifen and is also associated with clinical outcomes. However, despite adjusting for CYP2D6 genotype, large variability in the circulating levels of endoxifen are still observed, indicating that additional mechanisms, such as other metabolizing pathways, are involved. The UDP-glucuronosyltransferases (UGT) are a super family of phase II metabolizing enzymes that conjugate a glucuronic acid moiety to a substrate, increasing the polarity and thereby facilitating excretion. The present dissertation identified UGTs 1A8, 1A10, and 2B7 as the most active UGTs against trans-endoxifen, in vitro. In addition, UGT2B7 genotype is associated with the glucuronidation phenotype of human liver microsomes (HLM) against both trans-endoxifen and trans-4-OH-TAM. HLM specimens that were hetero- or homozygous for the polymorphic UGT2B7^268Tyr allele exhibited a significant decrease in the glucuronidation of trans-endoxifen and trans-4-OH-TAM. A previous study reported the phosphorylation of UGT2B7 by the non-receptor tyrosine kinase, Src, which altered UGT2B7 enzyme activity against the endogenous substrate, 4-hydroxy-estrone. Therefore, the effect of over-expression of Src in UGT2B7 cells on the glucuronidation of trans-endoxifen and trans-4-OH-TAM was examined. Stable over-expression of Src in the wildtype UGT2B7 cells resulted in a significant decrease in the glucuronidation of both TAM metabolites, similar to the level observed in cell lines only stably expressing the polymorphic UGT2B7 ^268Tyr. Interestingly, over-expression of Src in the variant UGT2B7 ^268Tyr cell line did not alter glucuronidation activity. The evidence presented in this dissertation provides additional knowledge of the metabolism of TAM and specifically, how the pharmacogenetics of the UGT family of phase II metabolizing enzymes cause inter-individual differences in TAM metabolism.