Cyclin dependent protein kinases (CDKs) play vital role in gene expression and cell cycle regulation. CDKs require cyclin binding activity, phosphorylation through CDK activating kinase (CAK), Cdc25, Wee 1 kinase. Non-cyclin CDK activators include CDK5 activators, Viral Cyclins and RINGO/Speedy. Among all CDK activators, CAK carries prime importance. The time frame of activating phosphorylation varies across different model organisms. A literature search was performed via using Keywords: Cyclin-dependent kinases, CDK activating kinases, Interactions of CDK activating kinase, Association of CDK activating enzymes with cellular proteins, Cell cycle regulation via CDKs, Structure and Function of CDK activating kinases in Pubmed and Google scholar. The key findings on the basis of previous studies illustrated that the CDK3, CDK4 and CDK6 are associated with regulation of G1-S phase transition; CDK2 is involved in entrance to S phase and DNA replication; while CDK1 is vital for mitosis. The CDK activity is regulated via cyclin binding, cyclin-dependent kinase inhibitors CKIs, CDK phosphorylation at ATP-binding pocket for inhibition while for activation CDK phosphorylation occurs at T-loop conserved residue. Structural and functional characterization of CDK activating kinases and interactions with other cellular proteins were also discussed in detail. Loss of CAK activity usually leads toward transcriptional defects and cell cycle arrest. Identification of CDK and CDK activating kinases inhibitors could provide potential therapeutic options against human neoplasias.