This review aims to summarize the available evidence on the efficacy and tolerability of sulthiame for different forms of epilepsy. The analysis of international publications suggests that sulthiame is considered as a first-line drug for the treatment of age-dependent epilepsy with central temporal spikes (rolandic epilepsy). Sulthiame is highly effective in children with epileptic encephalopathies manifesting with spike-and-wave activity during sleep, including Landau-Kleffner syndrome, as well as in patients with myoclonic seizures. The drug might be also effective in patients with other forms of focal epilepsy, including those resistant to therapy. The tolerability of sulthiame is higher that that of old antiepileptic drugs and even levetiracetam; thus, it is associated with a lower risk of treatment interruptions due to adverse events. Moreover, sulthiame can be used for behavioral disorders (such as hyperkinetic behavior, aggressiveness) and cognitive impairments. Sulthiame can be effective in patients with epilepsy and sleep apnea.