The interleukin-1 (IL-1) family of cytokines and receptors are implicated in the functioning of innate and adaptive immunity and the genesis of inflammation. They are widely expressed in structural and immune cells with marked expression within barrier mucosal surfaces. In the lung, gut and skin, which are common entry sites for pathogens, they play essential functions in maintaining the functional integrity of the barrier and manage innate and adaptive immunity in response to insult and infections. In tissue sites, the IL-1 cytokines are tightly regulated by mechanisms involving decoy receptors and protease degradation. Dysregulation of these processes are associated with aberrant tissue inflammation leading to a number of inflammatory diseases. This review will address the roles of the different IL-1 cytokines at the lung, gut and skin barrier surfaces at homeostasis, and their roles as inflammatory mediators in diseases such as asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, atopic dermatitis and psoriasis.