The smooth identification and low-cost production of highly specific agents that 
interfere with signaling cascades by targeting an active domain in surface 
receptors, cytoplasmic and nuclear effector proteins, remain important 
challenges in biomedical research. We propose that peptide aptamers can provide 
a very useful and new alternative for interfering with protein-protein 
interactions in intracellular signal transduction cascades, including those 
emanating from activated receptors for growth factors. By their targeting of 
short, linear motif type of interactions, peptide aptamers have joined nucleic 
acid aptamers for use in signaling studies because of their ease of production, 
their stability, their high specificity and affinity for individual target 
proteins, and their use in high-throughput screening protocols. Furthermore, 
they are entering clinical trials for treatment of several complex, pathological 
conditions. Here, we present a brief survey of the use of aptamers in signaling 
pathways, in particular of polypeptide growth factors, starting with the 
published as well as potential applications of aptamers targeting Epidermal 
Growth Factor Receptor signaling. We then discuss the opportunities for using 
aptamers in other complex pathways, including Wnt/β-catenin, and focus on 
Transforming Growth Factor-β/Smad family signaling.