A family of proteins designated cyclin dependent kinases (Cdks) are critical regulators of cell cycle progression. Cdk family members, including Cdc2 p34, Cdk1–9, PISSLRE, KKIALRE, PITSLRE, and PCTAIRE 1–3 are constitutively expressed throughout the cell cycle. Cdc2 p34 activity peaks during mitosis and Cdk2 activity rises in late G1 or early S phase. Cdk4 and Cdk6 are critically involved in G1 to S phase progression. The functions of Cdk3, Cdk5b, PISSLRE, KKIALRE and PCTAIRE 1–3 are less well defined. Cdk9 (also designated PITALRE) has been shown to specifically phosphorylate the retinoblastoma protein. The more recently cloned Drosophila protein, P-TEFb, is thought to be the homolog of mammalian PITALRE. P-TEFb has been shown to be required for HIV Tat transcriptional activation.