Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder 
caused by inactivating mutations in either the TSC1 or TSC2 genes. It is 
characterized by the development of multiple, benign tumors in several organs 
throughout the body. Lesions occur in the brain, kidneys, heart, liver, lungs, 
and skin and result in seizures and epilepsy, mental retardation, autism, and 
renal and pulmonary organ system dysfunction, as well as other complications. 
Elucidation of the molecular pathways and etiological factors responsible for 
causing TSC has led to a paradigm shift in the management and treatment of the 
disease. TSC1 or TSC2 mutations lead to constitutive upregulation of the 
mammalian target of rapamycin pathway, which affects many cellular processes 
involved in tumor growth. By targeting mammalian target of rapamycin with 
everolimus, an orally active rapamycin derivative, clinically meaningful and 
statistically significant reductions in tumor burden have been achieved for the 
main brain (subependymal giant cell astrocytoma) and renal manifestations 
(angiomyolipoma) associated with TSC. This review provides an overview of TSC, 
everolimus, and the clinical trials that led to its approval for the treatment 
of TSC-associated subependymal giant cell astrocytoma and renal angiomyolipoma.