The acquisition of anticancer drug resistance worsens the prognosis of cancer. Various studies have been conducted on the mechanism of drug resistance acquisition, but the results of these basic studies have not yet led to clinical applications such as the development of marker for drug resistance acquisition and the development of treatment method for drug sensitivity recovery. In these basic studies, there are many reports suggesting that changes in glycans on glycoproteins are one of the causes of resistance acquisition. In squamous cell carcinoma cell lines with acquired resistance to platinum drug, it is known that high mannose-type glycans increase and are involved in ERAD (glycoprotein degradation mechanism) [1]. Also, in breast cancer cell lines with acquired resistance to microtubule depolymerization inhibitors, it was found that increased glycosylation to P-glycoproteins, which functions in drug efflux, resulted in increased localization of P-glycoproteins to the plasma membrane and enhancing its function [2]. Furthermore, in leukemia cell lines with resistance to microtubule depolymerization inhibitors, it has been reported that all protein glycans on the cell membrane have decreased α2,6-sialic acid [3]. The decrease in α2,6-sialic acid in resistant cells may allow cancer cells to evade apoptosis [4]. On the contrary, it was found that breast cancer cell lines expressed a lot of mucin, which are high molecular weight glycoproteins and have hydrophilic barrier function on the cell surface, resulting in acquisition of resistance to lipophilic anticancer drugs [5] (Fig. 51.1). From these results, it is very important to search for markers that can diagnose the acquisition of drug resistance and therapeutic target molecules that can recover sensitivity.