Growth factor receptors that are tyrosine kinases (RTKs) regulate growth and differentiation of cells in many organisms, including flies, worms, frogs, mice and humans. There has been recent progress in understanding the mechanism by which these receptors transduce signals. Worm and insect studies on RTKs have relied primarily on genetics, while the mammalian studies have employed a combination of molecular genetics and biochemistry. While many RTKs seem to have unique features, there are also many general signal transduction principles that emerge from these studies. In this review, we will focus on common signaling molecules, using RTKs from both vertebrates and invertebrates as examples.