Protein kinase Calpha (PKCalpha) is a serine/threonine protein kinase that has been implicated in the regulation of a variety of cellular functions such as proliferation, differentiation and apoptosis in response to a diverse range of stimuli. In order to execute these biological events PKCalpha activity is modulated by, and functionally interacts with, a number of proto-oncogenes, therefore it is perhaps unsurprising that dysregulation of PKCalpha is associated with a diverse range of cancers. Recently, PKCalpha has become a target for a number of anti-cancer therapies. The purpose of this review is to describe how PKCalpha regulates key biological events, to gain an insight into how PKCalpha-mediated cellular transformation may occur. In this way, it may be possible to design therapeutic tools to combat cancers specifically associated with PKCalpha dysfunction.