Studies of signal transduction are often focused on dissecting the cellular response to a single stimulus that activates a single receptor. These types of studies laid the foundation for our current understanding of signaling, as well as the generation of countless arrow-containing models in today's textbooks. Implicit in most models is the suggestion that the arrows emanating from an activated receptor represent the core signaling pathways that are always activated by a given receptor, thus leading to a core cellular response. In nature, however, it is likely that no signaling pathway is activated in isolation. Rather, cells often respond to multiple stimuli simultaneously, and the cellular response may be the result of several signaling pathways. A new study attempts to model such conditions in vitro and reveals that when macrophages encounter bacteria, two signal transduction pathways interact in a way that profoundly alters the cellular response to infection.