Cancers are often intrinsically resistant or become resistant to treatment with conventional chemotherapy. This broad-spectrum resistance results in large part, but not solely, from overexpression of a variety of members of the ATP-binding cassette (ABC) superfamily of transport proteins. ABCG2 (ABCP/MXR/BCRP), as a half ABC transporter, is a novel member of the ABC membrane transporters, which can actively transport a wide spectrum of drugs with varying chemical structures or cellular targets. ABCG2 is overexpressed in the intestine, liver, placenta, and the blood-brain barrier, where it plays a role in protecting the organs from potentially harmful ingested toxins. Moreover, ABCG2 is also highly expressed in hematopoietic stem cells, it seems that ABCG2 has a key function in stem cell regulation or protection from a variety of xenobiotics. Multiple of SNP (single nucleotide polymorphisms) in ABCG2 may affect absorption and distribution, altering the effectiveness and toxicity of drugs in patients. Like other members of the ABC transporter superfamily, such as MDR1 and MRP1, ABCG2 is expressed in a variety of malignancies. Overexpression of ABCG2 in tumor cells confers cancer multidrug resistance to a variety of newly developed anticancer drugs including mitoxantrone, topotecan, epirubicin, anthracyclines and camptothecins. Furthermore, ABCG2 are advocated for use as potentially selectable markers in stem cell based gene therapy. Given the profound impact of ABCG2 on multidrug resistance in tumor cells and on in vivo pharmacology and toxicology, a complete understanding of the mechanism and biological function of ABCG2 will be important for understanding its normal physiology as well as potentially for the development of novel chemotherapeutic treatment strategies. The discovery, the biochemistry, the normal physiology and the current insight of human ABCG2 were introduced.