The 2014 American Academy of Pediatrics bronchiolitis guidelines do not adequately serve the needs and clinical realities of front-line clinicians caring for undifferentiated wheezing infants and children. This article describes the clinical challenges of evaluating and managing a heterogeneous disease syndrome presenting as undifferentiated patients to the emergency department. Although the 2014 American Academy of Pediatrics bronchiolitis guidelines and the multiple international guidelines that they closely mirror have made a good faith attempt to provide clinicians with the best evidence-based recommendations possible, they have all failed to address practical, front-line clinical challenges. The therapeutic nihilism of the guidelines and the dissonance between many of the recommendations and frontline realities have had wide-ranging consequences. Nevertheless, newer evidence of therapeutic options is emerging and forecasts hope for more therapeutically optimistic recommendations with the next revision of the guidelines.