A challenge in the development of inhibitors of intracellular targets is to achieve specificity and high affinity for those targets. Here peptides, that can mimic specific protein-protein interaction surfaces, can provide the answer, so long as cell permeability and stability issues are addressed. Here we describe progress in developing a specific inhibitor of the Grb7-SH2 domain involved in cancer progression. Grb7 is an adapter protein, aberrantly co-overexpressed with erbB-2 and identified as an independent prognostic marker in breast cancer. Grb7 signals the activation of erbB-2 and erbB-3, which play key roles in disregulated cell growth in cancer. Grb7 also mediates signalling pathways from another tyrosine kinase, focal adhesion kinase (FAK) exacerbating cell migration and the metastatic potential of cells. It is thus a prime target for the development of novel anti-cancer therapies. We have characterised a non-phosphorylated cyclic peptide (G7-18NATE) that is a specific inhibitor of Grb7 and inhibits cellular growth and migration in cancer cell lines. X-ray crystallographic structure determination of the G7-18NATE/Grb7-SH2 domain complex and binding studies using surface plasmon resonance have revealed the basis of affinity and specificity of the peptide1-3. Here we describe how this information has been used to successfully design second generation bicyclic peptides that show enhanced binding without loss of specificity. These peptides can be coupled to cell penetrating peptide sequences to be taken up by cells, lowering cell growth and migration. We anticipate that these Grb7 inhibitor peptides will form the basis of novel therapeutics that can be used in conjunction with existing therapies against breast cancer.