The present invention provides methods of using cord blood and cord blood-derived stem cells in high doses to treat various conditions, diseases and disorders. The high-dose cord blood and cord blood-derived stem cells have a multitude of uses and applications, including but not limited to, therapeutic uses for transplantation and treatment and prevention of disease, and diagnostic and research uses. In particular, the cord blood or cord blood-derived stem cells are delivered in high doses, e.g., at least 3 billion nucleated cells per treatment, where treatment may comprise a single or multiple infusions. The invention also provides for the use of cord blood or cord blood-derived stem cells from multiple donors without the need for HLA typing.