Reliable inter- and intracellular communication is central to both the development and the integrity of multicellular organisms. Key mediators of these processes are cell surface receptors that perceive and convert extracellular cues to trigger intracellular signaling networks and ultimately a phenotypic response. Deregulation of signal transduction leads to a variety of diseases, and aberrations in receptor proteins are very common in various cancer types. Therefore, cell surface receptors have been established as major targets in drug discovery. However, in order to efficiently apply therapeutics, it is crucial to gain knowledge about design principles of receptor signaling. In this chapter, we will discuss signal transduction at the receptor level for examples from different receptor classes.