Multidrug resistance impacts negatively upon the curative effect of chemotherapy and prognosis in colorectal cancer. There is a growing body of studies trying to develop drugs to overcome multidrug resistance against its common targets， including ATP-binding cassette proteins， metabolic enzymes， apoptotic genes， signaling pathways and genetic material， among which P-glycoprotein inhibitors and drugs disrupting DNA are deeply developed. Developing new inhibitors or combining existing inhibitors with conventional treatment are hopeful ways to overcome multidrug resistance in colorectal cancer.