Do kinases cascade? How well is cell regulation understood? What are the best ways to model regulatory systems? Attempts to answer such questions can have bearings on the way in which research is conducted. Fortunately there are recurring themes in regulatory processes from many different cellular contexts, which might provide useful guidance. Three principles seem to be almost universal: regulatory interactions are cooperative; regulatory decisions are made by large dynamic protein complexes; and regulation is intricately networked. A fourth principle, although not universal, is remarkably common: regulatory proteins are actively placed where they are needed. Here, I argue that the true nature of cell signalling and our perceptions of it are in a state of discord. This raises the question: Are our misconceptions detrimental to progress in biomedical science?