Cyclin dependent kinase 9 (CDK9) plays an essential role in regulating transcriptional elongation. Aberrations in CDK9 activity have been observed in various cancers, which make CDK9 an attractive therapeutic target for cancers. This led to an intensive development of small-molecule CDK9 inhibitors or new emerging strategies, such as proteolysis targeting chimeras (PROTACs). Here, we review the CDK9 modulators in cancer not only for research purposes, but also for therapeutic applications.