Over the past three decades, research exploring potential neuronal replacement therapies have focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. Over most of the past century of modern neuroscience, it was thought that the adult brain was completely incapable of generating new neurons. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain, and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent findings from our lab demonstrate that it is possible to induce neurogenesis de novo in the adult mammalian brain, particularly in the neocortex where it does not normally occur, and that it may become possible to manipulate endogenous multipotent precursors in situ to replace lost or damaged neurons. Recruitment of new neurons can be induced in a region-specific, layer-specific, and neuronal type-specific manner, and newly recruited neurons can form long-distance connections to appropriate targets. Elucidation of the relevant molecular controls may both allow control over transplanted precursor cells and potentially allow the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that do not require transplantation of exogenous cells.