Cyclin-dependent kinases (CDKs) are perceived as the engine that drives cell cycle progression whereas cyclins are considered to be the gears that are changed to aid the transition between cycle phases. Cyclin-dependent kinase 14 (CDK14) is a cdc2-related serine/threonine protein kinase and plays an important role in normal cell cycle progression. CDK14 and other TAIRE family kinases (CDKs 15-18) are frequent off-targets of clinical kinase inhibitors. CDK14 has significant involvement in tumorigenesis of cancers including hepatocellular carcinoma, gastric carcinoma and breast cancer. In esophageal cancer, CDK14 is useful as a prognostic marker and as a predictor of response to chemotherapy.