The articles in this miniseries of reviews concentrate on signaling and apoptotic cascades that are modulated by virus infection of the CNS. They underscore the cross talk between various signaling cascades, their susceptibility to virus regulation and their contribution to disease pathogenesis in humans. The first article (Aurelian) provides a brief summary of present understanding of apoptotic and signaling cascades. It underscores cross talk and the integration of different signals in neuronal pathogenesis. The second article (Perkins) reviews the various strategies used by viruses to commandeer signaling pathways and apoptosis cascades in infection of the central nervous system. The third article (Gober et al.) discusses apoptosis regulatory genes and their co-option by virus infection. Focus is on the heat shock proteins (Hsp), a versatile family that bridges signaling cascades and the immune system. The last article in this series (Smith) uses a herpes simplex virus type 2 (HSV-2) protein known as ICP10PK as a model to examine virus-mediated modulation of signaling cascades underscoring the role of the cell type and its mitotic state.