The PIM Kinases belong to the family of a proto-oncogene that essentially phosphorylates the serine/threonine residues of the target proteins. They are primarily categorized into three types PIM-1, PIM-2, PIM-3 which plays an indispensable regulatory role in signal transduction cascades, by promoting cell survival, proliferation, and drug resistance. These kinases are overexpressed in several solid as well as hematopoietic tumors which supports in vitro and in vivo malignant cell growth along with survival by regulating cell cycle and inhibiting apoptosis. They lack regulatory domain which makes them constitutively active once transcribed. PIM kinases usually appear to be important downstream effectors of oncoproteins which overexpresses and helps in mediating drug resistance to available agents, such as rapamycin. Structural studies of PIM kinases revealed that they have unique hinge regions where two Proline resides and makes ATP binding unique, by offering a target for an increasing number of potent PIM kinase inhibitors. Preclinical studies of those inhibitory compounds in various cancers indicate that these novel agents show promising activity and some of them currently being under examination. In this review, we have outlined PIM kinases molecular mechanism and signaling pathways along with matriculation in various cancer and list of inhibitors often used.