Historically, before the advent of modern imaging and genetic testing, Tuberous Sclerosis Complex (TSC) was more of a diagnostic challenge and less of a treatment challenge. This is because the natural history of TSC was poorly understood and TSC-specific treatments were non-existent. In the current era, diagnosis is more straightforward but management is much more complex. Disease manifestations vary by age, severity, and organ system. Management issues in the first few months of life, including neurologic manifestations, are very different than late childhood, adolescence, and adulthood. With increasing numbers of TSC diagnoses being made prenatally or shortly after birth, the opportunity for interventions that may improve long-term developmental and epilepsy outcomes now may precede the onset of neurological clinical symptoms. Familiarity and anticipation of these neurologic complications and rapid response to their emergence is crucial. Periodic imaging surveillance for development of subependymal giant cell astrocytoma (SEGA), preferably by magnetic resonance imaging (MRI) every 1-3 years, is now standard of care. Early SEGA detection provides opportunity to initiate pharmacologic treatment with everolimus if appropriate, thereby negating the need for invasive surgery. Routine electroencephalography (EEG) in asymptomatic infants for the first year or two of life is becoming increasingly accepted, with treatment initiation of vigabatrin dependent on concerning EEG findings instead of waiting until onset of clinical seizures, the traditional approach. Effective SEGA treatment and optimal seizure control remain principal during the first few decades of life for the clinical neurologist involved in the management of TSC. However, during the same period and extending through adulthood, assessment of TSC-associated neuropsychiatric disorder (TAND) is also key to the best clinical outcome and quality of life for affected individuals and their surrounding family and caregivers.