Hematopoietic stem cells (HSCs) are found in yolk sac, fetal liver, umbilical cord blood, placenta, and amniotic fluid during mammalian embryonic development. In adults, HSCs reside in marrow cavity of long bones where they self-renew and differentiate to replenish short-lived mature blood cells. HSCs exist in very low frequencies within specific "niches" where they interact with the surrounding environment through molecular associations. Overall HSC function can last much longer than a normal lifetime, but HSCs do show functional senescence with characteristic features of decreased self-renewal, reduced clonal stability, reduced homing and engraftment, and biased lineage commitment. The progressive shortening of telomeres with increasing age, especially under conditions with specific mutations in the telomerase gene complex, could predispose patients to HSC dysfunction and bone marrow failure diseases. Continuous investigation into HSC biology should facilitate the utilization of HSCs as a therapeutic modality and helps to prevent HSC malfunction.