In the last few decades, cancer chemotherapy has seen major medical advances. However, multidrug resistance (MDR), due to overexpression of ATP-binding cassette (ABC) transporters is a major impediment in the process of cancer treatment. ABC transporters lead to MDR by actively effluxing various amphipathic compounds, causing decreased intracellular drug accumulation in a patient’s tumor cells. Conventionally, pharmacological development of synthetic molecules or identification of natural products that block ABC transporter-mediated efflux have been sought to combat MDR. Although,the strategy is attractive due to its simplicity, clinical success with these chemosensitizers has been marginal. Therefore, newer approaches to identify or synthesize one or more ABC transporters, such as selective resensitizers with limited nonspecific toxicity, have been undertaken. This review briefs the current advances in modulators and strategies being applied to resensitize chemotherapeutics in ABC transporters-mediated MDR tumors.