In direct lineage conversion, a differentiated cell is converted to another type of differentiated cell through forced expression of a small number of transcription factors. This approach has been used to turn mouse and human fibroblasts into several generic cell types, such as neurons and cardiomyocytes, but little progress has been made in generating more-specialized cell types. A recent study by Son et al. describes the conversion of mouse and human fibroblasts to motor neurons—a neural subtype of special interest because of its role in spinal muscular atrophy and amyotrophic lateral sclerosis. The authors' strategy was to combine transcription factors previously shown to convert fibroblasts to generic neurons with a second set of transcription factors known to be important in motor neuron development. In mouse embryonic fibroblasts, expression of an 11-factor cocktail generated cells resembling motor neurons, and the 11 factors could be whittled down to 7. These seven factors and one additional factor were then used to generate motor neurons from human fibroblasts. The induced motor neurons resembled their embryo-derived counterparts with respect to morphology, transcriptional profiles, electrophysiological activity, in vivo engraftment and responses to degenerative stimuli. (Cell Stem Cell 9, 205–218, 2011)