Systemic amyloidosis is a hereditary or acquired disease characterized by deposition of amyloid insoluble fibrils into body organs and tissues, causing structural abnormalities and organ dysfunction, i.e. heart failure. This disease is classified according to the precursor protein involved; immunoglobulin light chains, transthyretin and apolipoprotein A1 underlie the cardiac involvement. Amyloid cardiomyopathy is characterized by symmetric biventricular hypertrophy, preserved systolic function, and pronounced diastolic dysfunction. Although transthyretin-related cardiac amyloidosis has always been considered a rare disease, in the last few years it has been found to be one of the most common causes of hypertrophic cardiomyopathy, thanks to better diagnostic algorithms and considerable improvements in cardiac imaging. Achieving an early diagnosis is a challenge for the modern cardiologist since new disease-modifying therapies have been developed in recent years. This article aims to answer to the main questions about transthyretin-related cardiac amyloidosis: when to suspect it, how to diagnose it and how to treat it.