Purinergic signalling has been implicated in many biological processes, and ATP and other extracellular nucleotides might have therapeutic potential in the treatment of cancer by signalling through P2 receptors. Different P2 receptor subtypes have been identified in a variety of different cancer types, in both primary samples of human cancer tissue and cell lines. Recent evidence suggests that different receptor subtypes mediate different pathophysiological functions such as proliferation, differentiation and apoptosis. In vivo studies of the use of ATP suggest that it can decrease the rate of cancer growth, and the first clinical trials have been undertaken. Thus, agents acting at P2 receptors might provide novel therapeutic tools in the treatment of cancer. In this article, background information about purinergic signalling and purinoceptor subtypes will be provided and then the proposed role of ATP in different cancers will be discussed in detail, including a discussion of in vivo studies and animal models, clinical trials and the specific P2 receptor subtypes involved.