 Cancer drug resistance remains a significant challenge for medical oncologists. Different mechanisms enable tumors to evade treatments such as alterations in drug transport and metabolism, mutation and amplification of drug targets and changes in cellular signaling pathways. Additionally, tumor heterogeneity can lead to the emergence of small sub-populations of cells with resistance to certain drugs. Finally, multi-drug resistance can further complicate the issue, making it increasingly difficult to treat cancer patients. Understanding these mechanisms can help inform future strategies for overcoming drug resistance. This article was authored by Hiba Izzaridine and Catherine E. Borden.