OPINION STATEMENT: Infantile spasms (IS) represent a major therapeutic challenge, as cessation of spasms and normalization of the electroencephalogram (elimination of hypsarrhythmia) are mandatory to prevent cognitive deterioration in previously healthy infants, or to preserve neurocognitive function among those neurologically affected prior to onset of IS. Traditionally, this epilepsy syndrome has been considered a "catastrophic" epilepsy, not only for its frequent refractoriness, but mostly due to its effect on cognition. Nevertheless, a change of attitude among pediatric epileptologists is probably warranted, as enough evidence and clinical experience demonstrate that early, aggressive therapy, especially with adrenocorticotropic hormone (ACTH), may not only lead to cessation of spasms, but often leads to the cure of infants with idiopathic/cryptogenic IS. Some ACTH protocols such as that prescribed in Israel (tetracosactide ACTH) appear to be highly efficacious in guarantying a good or even excellent prognosis in idiopathic IS. Moreover, oral prednisolone is a promising and much less expensive alternative to IM ACTH. Vigabatrin does have a role as a first-line agent, especially for tuberous sclerosis patients, but evidence supports hormonal therapy as the initial treatment. The role of pyridoxine and the ketogenic diet still needs to be established; given the efficacy of a much shorter tetracosactide ACTH protocol, there may be no need for the long-term diet, despite its efficacy. Finally, a very promising drug has been developed (CP-115) that may altogether replace the current therapeutic regimens in the near future.