After G protein-coupled (GPC) receptors, protein kinases are considered as most important drug targets. Kinase family consists of multigene, which is particularly relevant to various diseases. Protein phosphorylation by kinases plays a crucial activity in many cellular processes like apoptosis, cell division, survival, metabolism, etc. The emergence of various protein kinases crystal structures from many research groups gives a deep insight to understand the catalysis and regulation of different protein kinases. This review will mainly focus on the active site structures and functions of few kinases related to different families such as Protein A, G, and C kinase family (AGC), Ca2+/Calmodulin-dependent kinase family (CaMK), Cyclin-dependent kinase family (CMGC), Receptor guanylatecyclase family (RGC), Tyrosine kinase family (TK), Tyrosine kinase-like family (TKL), Sterile 20 Serine/threonine kinase family (STE), and Casein kinase 1 family (CK1).