During the last two decades nitric oxide (NO) produced by inducible NO synthase (iNOS or NOS2) has been characterized as immunoregulatory and antimicrobial principle displaying the potential to determine course of disease in a range of infections. Being an enzyme primarily regulated on expressional level, cytokine‐driven iNOS appears to be connected in particular with activation of Th1‐type immunity. However, with the recent advent of additional, partly overlapping CD4⁺ T cell effector subsets, namely Th17 and Th22 cells, a further layer of complexity has been added to immunoregulatory networks determining inflammatory gene expression in the context of microbial infections. Here, we review current knowledge on activation of iNOS function by interleukin (IL)‐17 and IL‐22 with focus on Th17/Th22‐directed antibacterial immunity.