Lennox-Gastaut syndrome (LGS) is one of the intractable epilepsies of childhood that is associated with an epileptic encephalopathy. Although LGS has been accepted as a distinct epilepsy syndrome for the last 30 years, understanding of its pathogenesis is still incomplete. Because this heterogenous entity has many diverse etiologies, some with specific therapy, a complete evaluation is necessary. The natural history is well defined; most children with LGS will ultimately be mentally retarded, will continue to have seizures, and as adults will be dependent for their daily care. Therefore, their only hope is new therapies and advances in our understanding of the pathogenesis of LGS. Several new treatment options have emerged. For the first time in the last 20 years, we have several medications with documented efficacy. In addition, there are effective nonpharmacologic treatments. These treatments offer the potential for improved seizure control, which we hope will have impact and lessen the subsequent epileptic encephalopathy. Children with LGS require multidisciplinary assessment and treatment along with vigorous intervention aimed at minimizing their seizures to maximize their potential. Pediatric neurologists should be familiar with the treatments with proven efficacy, including new antiepileptic drugs, and should develop a rational plan of treatment for each child with LGS.