Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.