The vasoactive regulatory peptides produced by neural and endothelial tissues contribute to normal vascular function and can modify the inflammatory process. Modern microscopic imaging techniques are revealing the plasticity of this neurovascular peptidergic system, highlighting changes in the synthesis, release, binding and degradation of vasoactive peptides during the inflammatory process. Initial changes may represent normal protective mechanisms against tissue injury, while subsequently a loss of neurovascular regulation may contribute to the pathogenesis of some inflammatory conditions. Understanding the complexity of these regulatory systems provides novel insights into the inflammatory process and suggests new possibilities for therapeutic approaches to human disease. In this review we examine the potential for modern microscopic imaging techniques to help elucidate the complexity of the inflammatory process, as illustrated by the involvement of the vasoactive neural- and endothelial-derived regulatory peptides substance P, calcitonin gene-related peptide, neuropeptide Y and endothelin.