Multidrug resistance (MDR) in cancer cells is a major challenge in effective chemotherapy. Cancer cells can resist multiple drugs through various mechanisms, including impaired drug delivery, genetic and epigenetic alterations, and the activation of detoxifying systems. ATP-dependent transporters, such as the ATP-binding cassette (ABC) transporters, play a key role in MDR by effluxing drugs from cells. Key ABC transporters include MDR1 (ABCB1), MRP1 (ABCC1), and ABCG2, which are expressed in many cancers and can influence treatment outcomes. Inhibitors of these transporters have been tested in clinical trials, but their effects on drug pharmacokinetics complicate interpretation. Future research should focus on developing specific inhibitors with minimal off-target effects and using surrogate assays to evaluate their efficacy. ABC transporters are also involved in normal physiological functions, such as protecting organs from toxins. In cancer, their overexpression contributes to drug resistance, and strategies to prevent their induction may help reduce resistance. Clinical trials have shown that PGP inhibitors can improve chemotherapy outcomes in some cancers, but challenges remain in determining their effectiveness. Surrogate assays, such as measuring PGP inhibition in cell lines or using imaging techniques, are being developed to assess the in vivo efficacy of these inhibitors. Overall, understanding the mechanisms of MDR is crucial for improving chemotherapy outcomes and developing more effective treatments.Multidrug resistance (MDR) in cancer cells is a major challenge in effective chemotherapy. Cancer cells can resist multiple drugs through various mechanisms, including impaired drug delivery, genetic and epigenetic alterations, and the activation of detoxifying systems. ATP-dependent transporters, such as the ATP-binding cassette (ABC) transporters, play a key role in MDR by effluxing drugs from cells. Key ABC transporters include MDR1 (ABCB1), MRP1 (ABCC1), and ABCG2, which are expressed in many cancers and can influence treatment outcomes. Inhibitors of these transporters have been tested in clinical trials, but their effects on drug pharmacokinetics complicate interpretation. Future research should focus on developing specific inhibitors with minimal off-target effects and using surrogate assays to evaluate their efficacy. ABC transporters are also involved in normal physiological functions, such as protecting organs from toxins. In cancer, their overexpression contributes to drug resistance, and strategies to prevent their induction may help reduce resistance. Clinical trials have shown that PGP inhibitors can improve chemotherapy outcomes in some cancers, but challenges remain in determining their effectiveness. Surrogate assays, such as measuring PGP inhibition in cell lines or using imaging techniques, are being developed to assess the in vivo efficacy of these inhibitors. Overall, understanding the mechanisms of MDR is crucial for improving chemotherapy outcomes and developing more effective treatments.