Although the concept of Syndrome X was introduced in the Banting Medal address of 1988 (Reaven, 1988), the notion that led to its genesis had started approximately 50 years earlier. In this short history, an attempt will be made to trace the two paths of scientific discovery that were formally merged in New Orleans in 1988 to form the scientific foundation of Syndrome X. In addition, the developments in the last 16 years that have led from the notion of Syndrome X to the broader concept of an Insulin Resistance Syndrome (IRS) will be briefly summarized.