Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant neurocutaneous disorder secondary to mutations in the TSC1 or TSC2 tumor suppressor genes. Although manifestation of the classic triad of seizures, intellectual disability, and facial angiofibromas may facilitate timely diagnosis of TSC, the multisystem features that may indicate TSC in the absence of these manifestations remain highly variable. In addition, patients with TSC are at risk of developing multiple benign and malignant tumors in various organ systems, resulting in increased morbidity and mortality. Thus, imaging plays a critical role in diagnosis, surveillance, and management of patients with TSC. It is crucial that radiologists be familiar with TSC and the various associated imaging features to avoid a delayed or incorrect diagnosis. Key manifestations include cortical dysplasias, subependymal nodules, subependymal giant cell astrocytomas, cardiac rhabdomyomas, lymphangioleiomyomatosis, and angiomyolipomas. Renal angiomyolipomas in particular can manifest with imaging features that mimic renal malignancy and pose a diagnostic dilemma. Other manifestations include dermatologic and ophthalmic manifestations, renal cysts, renal cell carcinomas, multifocal micronodular pneumocyte hyperplasia, splenic hamartomas, and other rare tumors such as perivascular epithelioid tumors. In addition to using imaging and clinical features to confirm the diagnosis, genetic testing can be performed. In this article, the molecular pathogenesis, clinical manifestations, and imaging features of TSC are reviewed. Current recommendations for management and surveillance of TSC are discussed as well. ©RSNA, 2021.