Protein kinase C (PKC) is a family of serine/threonine kinases involved in the transduction of signals that control different cellular processes, such as cell death and proliferation. This family comprises at least 10 isoforms that regulate apoptosis in an isoformspecific manner. However, controversial data about the role of individual PKC isoforms in apoptosis regulation are frequently reported. The co-existence of several PKC isoforms in a same mammalian cell, the distinct expression profile of PKC isoforms in different cell types, and the different stimulus applied may explain such contradicting results. Therefore major advances in the understanding of the molecular mechanisms that regulate the function of PKC isoforms in apoptosis are still required. Yeast has proved to be a valuable research tool to investigate molecular aspects of apoptosis regulation. Additionally, the conservation in yeast of major functional and molecular properties of mammalian PKC isoforms favours the use of this simpler cell model to uncover relevant aspects of apoptosis regulation by this kinase family. In this review, we cover the current knowledge about the role of different PKC isoforms in apoptosis. Moreover, we discuss the contribution of yeast to unravel several controversial issues about apoptosis regulation by PKC isoforms. The exploitation of yeast cells expressing individual PKC isoforms towards the identification of isoform-specific PKC modulators is also discussed. The studies here summarised highlight that the yeast cell model system can provide valuable insights in the PKC research field.