The conversion of mouse skin fibroblasts directly to neurons was recently demonstrated, and now Asa Abeliovich and colleagues report the conversion of human skin fibroblasts from individuals with Alzheimer's disease (AD) directly into functional neurons (Cell 146, 359–371, 2011 ). Viral co-transduction of human skin fibroblasts with the three factors sufficient for neuronal reprogramming in mouse was ineffective. However, co-transduction with two additional transcriptional regulators in the presence of neural survival factors led to the generation of neuronal-like cells (human-induced neuronal cells, or hIN cells). Further experiments showed that ASCL1, BRN2 (also called POU3F2) and ZIC1 were sufficient to convert human fibroblasts to hIN cells. To test whether reprogramming was directed or requires passage through a progenitor state, the authors looked at expression of Sox2 and Pax6 and found no evidence of a neuronal progenitor state. hIN cells possessed physiological properties of typical neurons and could integrate into neuronal circuits in vitro and in vivo. hiN cells from individuals with familial AD showed an increased Aβ42/Aβ40 ratio, consistent with phenotypes seen in persons with AD. The authors note that these experiments validate the utility of patient-derived cell models of neurodegenerative diseases and suggest that future work should focus on testing whether hIN cells from AD patients integrate into neuronal circuits in vivo.