Significant advances in cancer treatment have resulted from the targeted cancer therapy by understanding the process of malignant transformation. Polo-like kinase 1 (PLK1) has been investigated as a target for cancer therapy for several years. Recently, anticancer drug candidates targeting PLK1 have been developed. To investigate the significance of PLK1 inhibitors in cancer patients, the current clinical statuses of PLK1 inhibitors including BI 2536, volasertib, and GSK461364A were analyzed. Monotherapy with BI 2536, the first human study of PLK1 inhibitors, has been terminated now, but its combinational study is still available in several solid tumors. The second-generation PLK1 inhibitor volasertib has an improved pharmacokinetic profile, safety, and efficacy, which is currently being developed under phase I/II. GSK461364 has shown a greater sensitive antitumor effect in p53-mutated cancer compared with that of p53-wild type cancer cells in a preclinical study. However, it has to be coadministered with an anticoagulator because of the high incidence of venous thrombotic emboli in clinical studies. PLK1 inhibitors showed a favorable pharmacokinetic profile, safety, and efficacy in patients with solid tumors. Further investigation with the use of PLK1 inhibitors in cancer patients who have mutated p53 or Ras and a high level of PLK1 as biomarkers is needed to consider the context and evaluation criteria of therapy.