The signaling pathways controlling cell growth and differentiation are almost invariably altered in cancer. During the course of tumor progression, cancer cells acquire a number of characteristic alterations. These include the capacities to proliferate independently of exogenous growth-promoting or growth-inhibitory signals, to invade surrounding tissues and metastasize to distant sites, to elicit an angiogenic response, and to evade mechanisms that limit cell proliferation, such as apoptosis and replicative senescence. These properties reflect alterations in the cellular signaling pathways that in normal cells control cell proliferation, motility, and survival. These interconnected pathways are being deciphered, but understanding the alterations that lead to cancer and correcting them is a substantial challenge. Among the key pathways are those controlling cell proliferation, which coordinate a response to the cellular environment, with the mTOR kinase as a critical node. Tumour development is influenced by infections and inflammation, and the complex role of the nuclear factor-B transcription factors is being unravelled. Expansion of tumour cells depends on nutrient supply and vascularization, which is orchestrated by the transcription factor known as HIF. And the metastatic spread of primary tumours to other organs is facilitated by many signaling pathways.