To conclude, we have here presented a thorough literature review assessing the value of PDK1 in chemosensitization of cancer cells, analyzed Akt-dependent and independent pathways, and reported the available inhibitors up to date, while providing information on the preclinical validation of these inhibitors and the studies outcome, as well as the potential role of PDK1 as a pharmacodynamic biomarker. The gene discussed is PDK1; the disease is cancer.