This commentary discusses a retrospective study by Muzykewicz et al. that details EEG results from children with infantile spasms in the setting of tuberous sclerosis complex (TSC). In this study, several factors were identified as being predictive of poor cognitive outcome, including worsening degree of hypsarrhythmia, abnormalities in EEG background activity, and incomplete response to vigabatrin. Notably, the majority of patients had a poor outcome, experiencing cognitive impairment and intractable epilepsy irrespective of whether they were treated with adrenocorticotropic hormone (corticotropin) or vigabatrin, despite the fact that vigabatrin has shown promise in previous studies. However, among the entire cohort a third of patients enjoyed greater than 1 year of seizure freedom and about a quarter had either mild or no cognitive impairment at follow-up. Overall, these findings underscore the great challenges that are faced in the treatment of infantile spasms in patients with TSC. I suggest that, while vigabatrin has been shown to have impressive short-term efficacy, the intractable seizures and cognitive impairment in many patients with TSC strongly indicate that new therapies and treatment strategies are urgently needed.