<jats:title>Summary</jats:title><jats:p>Protein kinase <jats:styled-content style="fixed-case">C</jats:styled-content> constitutes a family of serine–threonine kinases found in all eukaryotes and implicated in a wide range of cellular functions, including regulation of cell growth, cellular differentiation and immunity. Here, we present three independent lines of evidence which indicate that protein kinase <jats:styled-content style="fixed-case">C</jats:styled-content> is essential for viability of <jats:styled-content style="fixed-case"><jats:italic>M</jats:italic></jats:styled-content><jats:italic>agnaporthe oryzae.</jats:italic> First, all attempts to generate a target deletion of <jats:styled-content style="fixed-case"><jats:italic>PKC</jats:italic></jats:styled-content><jats:italic>1</jats:italic>, the single copy protein kinase <jats:styled-content style="fixed-case">C</jats:styled-content>‐encoding gene, proved unsuccessful. Secondly, conditional gene silencing of <jats:styled-content style="fixed-case"><jats:italic>PKC</jats:italic></jats:styled-content><jats:italic>1</jats:italic> by <jats:styled-content style="fixed-case">RNA</jats:styled-content> interference led to severely reduced growth of the fungus, which was reversed by targeted deletion of the <jats:styled-content style="fixed-case">D</jats:styled-content>icer2‐encoding gene, <jats:styled-content style="fixed-case"><jats:italic>MDL</jats:italic></jats:styled-content><jats:italic>2</jats:italic>. Finally, selective kinase inhibition of protein kinase <jats:styled-content style="fixed-case">C</jats:styled-content> by targeted allelic replacement with an analogue‐sensitive <jats:styled-content style="fixed-case"><jats:italic>PKC</jats:italic></jats:styled-content><jats:italic>1<jats:sup>AS</jats:sup></jats:italic> allele led to specific loss of fungal viability in the presence of the <jats:styled-content style="fixed-case">PP</jats:styled-content>1 inhibitor. Global transcriptional profiling following selective <jats:styled-content style="fixed-case">PKC</jats:styled-content> inhibition identified significant changes in gene expression associated with cell wall re‐modelling, autophagy, signal transduction and secondary metabolism. When considered together, these results suggest protein kinase <jats:styled-content style="fixed-case">C</jats:styled-content> is essential for growth and development of <jats:styled-content style="fixed-case"><jats:italic>M</jats:italic></jats:styled-content><jats:italic>. oryzae</jats:italic> with extensive downstream targets in addition to the cell integrity pathway. Targeting protein kinase <jats:styled-content style="fixed-case">C</jats:styled-content> signalling may therefore prove an effective means of controlling rice blast disease.</jats:p>