Systemic acquired resistance (SAR) provides enhanced, long-lasting systemic immunity to secondary infection by a range of biotrophic, hemibiotrophic and necrotrophic pathogens that have diverse modes of infection. Considerable effort has focussed on the conserved central positive regulator of SAR, NON-EXPRESSOR OF PATHOGENESIS-RELATED1 (NPR1), and its control by changes in cellular redox potential. Recently, genetic and genomic approaches have highlighted a critical role for nucleocytoplasmic communication and protein secretion in establishing effective systemic immunity. Identification of the mobile signals and the mechanisms by which they are perceived in distal tissues remains challenging, but emerging evidence suggests that signal translocation uses lipid-derived (possibly jasmonate-based) signals and lipid-binding chaperones. Furthermore, the demonstration that autophagy interdicts and inactivates a systemic cell death signal adds further complexity to elucidating how mobile signals are decoded and transduced for effective immunity.