The article discusses the role of ATP-binding cassette (ABC) transporters, particularly ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2, in multidrug resistance (MDR) in cancer. Despite initial interest in these transporters as therapeutic targets, clinical trials targeting ABCB1 have largely failed. However, recent evidence suggests that ABC transporters may still play a role in clinical drug resistance. The authors argue that a better understanding of transporter biology and biomarkers could identify settings where these transporters are important therapeutic targets. They highlight the importance of ABC transporters in drug delivery, especially at the blood-brain barrier, and their role in resistance to chemotherapy. The article also discusses the complex role of transporters in MDR, including their expression in various tumor types and their impact on drug resistance. It emphasizes the need for further research to determine the clinical significance of ABC transporters in drug resistance and to develop effective therapeutic strategies. The authors conclude that while ABC transporters may not be the sole cause of MDR, they are important in certain contexts and that further investigation is needed to fully understand their role in cancer treatment.The article discusses the role of ATP-binding cassette (ABC) transporters, particularly ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2, in multidrug resistance (MDR) in cancer. Despite initial interest in these transporters as therapeutic targets, clinical trials targeting ABCB1 have largely failed. However, recent evidence suggests that ABC transporters may still play a role in clinical drug resistance. The authors argue that a better understanding of transporter biology and biomarkers could identify settings where these transporters are important therapeutic targets. They highlight the importance of ABC transporters in drug delivery, especially at the blood-brain barrier, and their role in resistance to chemotherapy. The article also discusses the complex role of transporters in MDR, including their expression in various tumor types and their impact on drug resistance. It emphasizes the need for further research to determine the clinical significance of ABC transporters in drug resistance and to develop effective therapeutic strategies. The authors conclude that while ABC transporters may not be the sole cause of MDR, they are important in certain contexts and that further investigation is needed to fully understand their role in cancer treatment.