The IL-1/IL-R and IL-36/IL-36R pathways share many features besides sequence and structural similarities unique that define the family of IL-1 and IL-1R cytokines. The IL-1R and IL-36R bind more than one agonist (i.e. IL-1α and IL-1β and IL-36α, IL-36β, and IL-36γ) as well as an antagonist, which is essential to balance the responses. Cytoplasmic proforms of the ligands are typically processed into mature forms with high activity. Moreover, they share a receptor accesory protein (IL-1RAcP) and the adaptor MyD88 which are critical for signaling. However, while IL-1α/IL-1β are highly pleitropic cytokines and their dysregulation is associated with many disease , the activity of IL-36 cytokines seem to be much more limited. Outstanding to date is their involvement in skin inflammation. In my presentation, I will highlight a few examples of inflammatory and infectious diseases, where my group has been addressing the roles of IL-1 and IL-36 cytokines.