Adverse drug reactions (ADRs) pose a significant challenge in clinical practice, impacting patient safety and treatment outcomes. Genetic variations in drug-metabolizing enzymes, particularly glutathione S-transferases (GSTs), have been implicated in modulating individual susceptibility to ADRs. This overview aims to explore the association between GSTs genetic polymorphisms and ADRs across diverse drug categories documented in current literature. Here we cover antiepileptic, immunosuppressive, chemotherapeutic agents, analgesics, antivirals, and antibiotics. According to the existing literature, the association between genetic polymorphisms in GST theta (GSTT1), GST mu (GSTM1), and GST pi (GSTP1) and adverse drug reaction occurrence has been frequently reported. However, the strength of these associations varies considerably among studies, with some showing inconsistent or contradictory results, underscoring the need for further investigations.

Tamoxifen remains the standard treatment for hormone-sensitive breast cancer. However, significant interindividual variability in treatment response is observed. This variability may be partially explained by differences in the biotransformation of tamoxifen, a prodrug, into its active metabolites. To address this, we conducted a comprehensive literature search across several databases to examine current evidence on single-gene and multi-gene variations throughout the metabolic and transport pathways of tamoxifen and their impact on pharmacokinetics and clinical efficacy. We also explore the influence of drug–drug–gene interactions and review clinical strategies currently employed to manage treatment variability. Overall, growing evidence highlights the influence of pharmacogenetic variability, particularly CYP2D6 polymorphisms, on tamoxifen metabolism. Although its clinical use remains cautious and limited, a combined approach involving pharmacogenetic testing and therapeutic monitoring or phenotyping may help address treatment variability.