Cyclin-dependent protein kinases (CDKs) play key roles in the progression of the cell cycle in eukaryotes. A CDK-activating kinase (CAK) catalyzes the phosphorylation of CDKs to activate their enzyme activity; thus, it is involved in activation of cell proliferation. In plants, two distinct classes of CAK have been identified; CDKD is functionally related to vertebrate-type CAKs, while CDKF is a plant-specific CAK having unique enzymatic characteristics. Recently, CDKF was shown to phosphorylate and activate CDKDs in Arabidopsis. This led to a proposal that CDKD and CDKF constitute a phosphorylation cascade that mediates environmental or hormonal signals to molecular machineries that control the cell cycle and transcription. In this review, we have summarized the biochemical features of plant CAKs and discussed the manner in which they diverge from animal and yeast orthologs. We have introduced several transgenic studies in which CAK genes were used as a tool to modify the CDK activity and to analyze cell division and differentiation during organ development.