Intracellular signaling pathways activated through cell surface receptors are essential for cell proliferation, differentiation, survival, and migration. Dysregulation of such signaling through mutations, chromosome rearrangements, aberrant gene expression, or epigenetic changes is a key factor in oncogenesis. Prominent examples of receptor signaling pathways that are dysregulated in cancers include those initiated by receptor tyrosine kinases, WNT, TGFbeta, and Notch receptors. In this review we will discuss these signaling pathways and how their dysfunction may contribute to oncogenesis. We will also highlight the important role of endocytic membrane trafficking in receptor signaling and tumor suppression.