Klinefelter syndrome (KS) is the most common chromosomal disorder in males, occurring in 0.1% to 0.2% of the general population, 3% of infertile males, and as high as 11% in non-obstructive azoospermia. Although KS has the classic features of small testes, hypogonadism, and infertility, less than 10% of children are diagnosed before puberty due to parental neglect regarding the development of their adolescent children. Most of them are found after marriage, due to infertility, so attention should be paid to KS in males during pubertal development. Approximately 80% of patients with KS are nonchimeric (47, XXY), with the remaining 20% having higher levels of chromosomal aneuploidy or chimerism. About 8% of adult KS men have spermatozoa present in their semen, and these men have typical occult azoospermia or severe oligozoospermia, and ICSI using ejaculate and testicular spermatozoa to obtain a pregnancy was reported abroad in 1998. In men with KS, youth is a positive predictor of sperm retrieval because the decline in testicular function secondary to KS is gradual, starting at puberty and becoming worse in adulthood. This is why frozen semen is routinely recommended for adolescents with spermatozoa present in the semen. It can make it possible to have the opportunity to have their own child at the time of childbearing. In KS infants, testosterone (T) levels are usually normal, and most KS boys have sufficient circulating T levels to initiate puberty, but often do not proceed adequately. Testosterone levels increase during early puberty, stabilize in the low to normal range during mid-puberty, and then decline. Due to progressive testicular steroid synthesis dysfunction, exogenous T supplementation is required during mid- to late puberty to complete full pubertal development and attain age-appropriate secondary sexual characteristics. Recommendations in current practice include initiating treatment in early to mid-puberty or at the onset of hypogonadism to ensure normal pubertal completion time and to prevent the symptoms and sequelae of long-term androgen deficiency. However, there are no specific guidelines on the optimal mode and timing of administration for patients with KS. Therefore more collaboration between disciplines such as pediatrics, endocrinology, male medicine, reproductive medicine, psychology and sociology should be established.