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Facilitated transport is necessitated for large size, charged, and/or hydrophilic drugs to move across the membrane. The drug transporters in the solute carrier (SLC) superfamily, mainly including organic anion-transporting polypeptides (OATPs), organic anion transporters (OATs), organic cation transporters (OCTs), organic cation/carnitine transporters (OCTNs), peptide transporters (PEPTs), and multidrug and toxin extrusion proteins (MATEs), are critical facilitators of drug transport and distribution in human body. The expression of these SLC drug transporters is found in tissues throughout the body, with high abundance in the epithelial cells of major organs for drug disposition, such as intestine, liver, and kidney. These SLC drug transporters are clinically important in drug absorption, metabolism, distribution, and excretion. The mechanisms underlying their regulation have been revealing in recent years. Epigenetic and nuclear receptor-mediated transcriptional regulation of SLC drug transporters have particularly attracted much attention. This review focuses on the transcriptional regulation of major SLC drug transporter genes. Revealing the mechanisms underlying the transcription of those critical drug transporters will help us understand pharmacokinetics and pharmacodynamics, ultimately improving drug therapeutic effectiveness while minimizing drug toxicity. It has become increasingly recognized that solute carrier (SLC) drug transporters play a crucial, and sometimes determinative, role in drug disposition and response, which is reflected in decision-making during not only clinical drug therapy but also drug development. Understanding the mechanisms accounting for the transcription of these transporters is critical to interpret their abundance in various tissues under different conditions, which is necessary to clarify the pharmacological response, adverse effects, and drug-drug interactions for clinically used drugs.