The regulation of neuronal differentiation and neurite outgrowth is essential during development of the nervous system and is crucial in developing therapies to promote axon regeneration after nerve injury or in neurodegenerative diseases. The serine/threonine kinase Akt has been well documented to promote neuronal survival. More recently Akt has also been revealed as key mediator of several aspects of neurite outgrowth, including elongation, branching and calibre. Downstream of Akt, several substrates have been identified that are likely to play key roles in Akt-mediated neurite outgrowth, such as glycogen synthase kinase 3beta, peripherin, mammalian target of rapamycin and delta-catenin. The physical interaction between Akt and Hsp27, another protein that has been linked with neurite outgrowth, may also be significant in the process of neurite outgrowth. This review will unite and discuss the research to date that has examined the functionality of Akt in neuronal differentiation during development and neurite outgrowth.