Aptamers are synthetic oligonucleotides selected from pools of random-sequence oligonucleotides which bind to a wide range of biomolecular targets with high affinity and specificity. Compared with antibodies, aptamers exhibit significant advantages including small size, easy synthesis and modification, as well as low immunogenicity. Many of the aptamers also show inhibition of their targets, making them potential therapeutic and targeting reagents in clinical applications. Compared with aptamers against intracellular proteins and molecules, however, the identification of aptamers against cell-surface receptors and receptor-related antigens is more difficult, due to the complex cellular environment in which receptors are located, and also the unique conformations and compositions of receptors to keep their activity. In this review, we will introduce the identification, modification and working mechanism of aptamers against cellsurface receptors. Based on the different characteristics of target receptors and selection strategies used, the identified aptamers show distinct binding affinity with recombinant targets or specific cell lines which express receptors on the surface in vitro. Some of the in vivo experiments also indicate that aptamers have the capability of inhibiting the overexpressing receptor-related tumor growth, working as potential anti-tumor therapeutic drugs. Despite of the difficulties during the selection of receptor aptamers and the study of their working mechanism during the present time, it is possible that in the future aptamers will increasingly exhibit therapeutic and diagnostic utility.