Abstract: Resistance to the cytotoxic actions of antineoplastic drugs remains a barrier to the establishment of curative chemotherapy regimens for cancer. Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene is the major molecular mechanism enhancing efflux pump for various anticancer agents, hence caused MDR. Transcription factor, DNA methylation, histone acetylation/deacetylation, phosphorylation and glycosylation and MDR1 gene polymorphisms play pivotal role in regulation of P-glycoprotein, and may become new therapeutic targets. This paper summarized the advances of studies on expression and regulation of P-glycoprotein.