The mitogen-activated protein kinase (MAPK) pathway provides cells with the means to interpret external signal cues or conditions, and respond accordingly. This cascade regulates many cell functions such as differentiation, proliferation and migration. Through modulation of both the amplitude and duration of MAPK signalling, cells can control their responses to the multiple activators of the pathway. In addition, recent work has highlighted the importance of the cellular compartment from which the signalling occurs. Cells have developed intricate systems that enable them to localise MAPK components to specific subcellular domains in response to a particular stimulus. Consequently, different factors can activate the same kinase in separate locations. Crucial to this ability are molecular scaffolds, which act as signalling modules for MAPKs, confining them to the desired compartment. The participation of the MAPK network in fundamental physiological processes, such as cell proliferation and inflammation, and the derangement of the homeostasis that occurs in disease processes, renders MAPK a highly desirable target for therapeutic intervention. As we enhance our comprehension of scaffolds and other regulatory molecules, novel targets for drug design may be discovered that will afford selective and specific MAPK modulation.