Genomic stability is integral for the continuation of life. The entire genome must be replicated only once during the synthesis phase of the cell cycle before a cell may progress into mitosis. Sophisticated safeguard mechanisms exist to regulate this critical process to prevent the development of aneuploidy and eventually cancer, two major consequences of deregulated DNA replication. One key regulator of DNA replication is Dbf4/Drf1-dependent kinase Cdc7 (DDK), which is necessary for the activation of DNA replication at individual origins of DNA replication (oris). Accumulating lines of data also suggest that DDK plays critical roles in the regulation of other cellular processes including meiosis, chromosome cohesion, checkpoint control, and mitotic exit. Because of its essential and diverse roles in the cell, DDK can be an excellent target for cancer therapy. Indeed, treatment of tumour cells with PHA-767491, a small molecule targeting Cdc7, caused apoptosis in vitro and inhibited tumour growth in animal models. We here summarize our current knowledge on the role of DDK in DNA replication and other cell cycle control mechanisms, which is akin to its famous cousins, cyclin-dependent kinases (CDKs). Finally, we discuss future directions in understanding the canonical and novel roles of DDK facilitated by differential regulation and consider the implications of DDK inhibition by pharmacological means based on the various roles it plays in the cell cycle.