In this review, we consider how the piriform cortex is engaged in both focal and generalized epilepsy networks and postulate the various neural pathways that can be effectively neuromodulated by stimulation at this site. This highlights the common involvement of the piriform cortex in epilepsy. We address both current and future preclinical studies of deep brain stimulation (DBS) of the piriform cortex, with attention to the critical features of these trials that will enable them to be of greatest utility in informing clinical translation. Although recent DBS trials have utilized thalamic targets, electrical stimulation of the piriform cortex may also be a useful intervention for people with epilepsy. However, more work is required to develop a solid foundation for this approach before considering human trials.