Klinefelter’s syndrome (KS;47XXY) is the most common sex chromosomal anomaly affecting 1:650 newborn males. The classic phenotype of tall stature, gynaecomastia and small testes occurs in adolescence / adulthood, with specific difficulties in learning and socialization frequently noted in childhood. Despite huge advances in medical knowledge over the years, the majority of affected males remain undiagnosed. The spectrum of disease in Klinefelter’s syndrome through the ages will be reviewed, together with treatment strategies including the current role of assisted reproductive technology.