Abstract: Phosphoinositide 3-kindase, an important signal transduction molecule in cells, plays a key role in the process of cell survival, proliferation and differentiation. Significant progress has been made in the treatment of cancer with PI3K inhibitors, yet the drug resistance of PI3K inhibitors affects their long-term efficacy in clinical treatment. In order to overcome the drug resistance, a variety of rational combined therapies have been developed. In this paper, the research progress of phosphoinositide-3 kinase inhibitors in combination with other drugs to overcome the drug resistance were reviewed.