Senile systemic amyloidosis (SSA) is a form of amyloidosis associated with aging, and is characterized by deposition of amyloid fibrils derived from wild-type transthyretin. Amyloid deposition is mainly seen in the myocardium, resulting in arrhythmia (atrial fibrillation) and/or heart failure. Previously, SSA was thought to represent a disease of aged patients over 80 years only; however, recent studies have indicated that SSA also affects much younger patients, with an onset around 50 years. In addition, a number of patients with SSA present with carpal tunnel syndrome (CTS), often several years prior to the onset of heart failure. Hence, CTS may be a key symptom suggestive of SSA, and amyloid deposits should always be confirmed in the operation specimens obtained during carpal tunnel release surgery in CTS patients aged over 50 years. Recently, effective drugs such as tafamidis and diflunisal, which stabilize the structure of the transthyretin tetramer, have been established in FAP patients, and therapeutic effectiveness of these drugs is also anticipated for SSA patients.