Appropriately chosen antiepileptic drug treatment can render around 70% of patients free of all seizures. However, around one-third will remain drug refractory despite polytherapy. Continuing seizures place patients at risk of SUDEP, depression, and reduced quality of life. Preventative strategies for SUDEP include reducing the occurrence of GTCS by timely referral for presurgical evaluation in people with lesional epilepsy and advice on lifestyle measures; detecting cardiorespiratory distress through clinical observation and seizure, respiratory, and heart rate monitoring devices; preventing airway obstruction through nocturnal supervision and safety pillows; reducing central hypoventilation through physical stimulation and enhancing serotonergic mechanisms of respiratory regulation using selective serotonin reuptake inhibitors (SSRIs); reducing adenosine and endogenous opioid-induced brain and brainstem depression.