Pentylenetetrazole (PTZ)-induced seizure is one of the gold standard mouse models for rapid evaluation of novel anticonvulsants. Synchronically, PTZ induced kindling in mice is also a simple and well accepted model of chronic epilepsy. PTZ kindling has been explored for studying epileptogenesis, epilepsy-associated comorbidities, and refractory epilepsy. This review summarizes the potential of PTZ kindling in mice and its modifications for its face, construct, and predictive validity to screen antiepileptogenic drugs, combined or add on novel and safe therapies for treatment of epilepsy-associated depression and cognitive impairment as well as effective interventions for pharmacoresistant epilepsy.