Cellular signaling pathways respond to external inputs to drive pivotal cellular decisions. Far from being mere data relay systems, signaling cascades form complex interacting networks with multiple layers of feedback and feed-forward control loops regulated in both space and time. While it may be intuitively obvious that this complexity allows cells to assess and respond appropriately to a myriad of external cues, untangling the wires to understand precisely how complex networks function as control and computational systems presents a daunting challenge to theoretical and experimental biologists alike. In this review we have focused on activation of the canonical MAP kinase cascade by receptor tyrosine kinases (RTKs) in order to examine some of the fundamental design principles used to build biological circuits and control systems. In particular, we explore how cells can reconfigure signaling cascades to generate distinct biological outputs by utilizing the unique spatial constraints available in biological membranes.