Epilepsy is characterized by seizures of diverse types that affect about 1-2% of the population worldwide. Current antiseizure medications are unsatisfactory, as they merely provide symptomatic relief, are ineffective in about one-third of patients, and cause unbearable adverse effects. Transient receptor potential canonical (TRPC) channels are a group of nonselective cation channels involved in many physiological functions. In this review, we provide an overview of recent preclinical studies using both genetic and pharmacological strategies that reveal these receptor-operated calcium-permeable channels may also play fundamental roles in many aspects of epileptic seizures. We also propose that TRPC channels represent appealing targets for epilepsy treatment, with a goal of helping to advance the discovery and development of new antiseizure and/or antiepileptogenic therapies.