The protein-protein interaction (PPI) between immunoglobulin E (IgE) and its high affinity receptor (FcεRI) is an important part of the allergic response. Inhibition of the IgE:FcεRI interaction is a key strategy for the development of allergy treatments. This PPI has been validated as a therapeutic target by the humanised monoclonal antibody omalizumab, which binds to IgE and prevents the formation of the IgE:FcεRI complex and has proved successful at treating allergic asthma. However, small molecule inhibitors of the IgE:FcεRI PPI that are orally available would be a more desirable form of treatment. This thesis describes the design, synthesis and testing of two series of inhibitors of the IgE:FcεRI interaction; small molecules based on the natural product aspercyclide A and short, linear peptides based on a key binding epitope of FcεRI. It also describes the development of a high-throughput time resolved fluorescence resonance energy transfer (TR-FRET) assay to test inhibitors and subsequent X-ray crystallography and SPR experiments to further investigate the mode of action of the inhibitors. An analogue of aspercyclide A has shown inhibition of the IgE:FcεRI interaction in the micromolar range and an improved potency compared to the natural product itself. A number of 8-residue, linear peptides have been found to inhibit the IgE:FcεRI PPI in the micromolar range when tested in the TR-FRET assay. The most potent peptide has been biotinylated and immobilised for SPR experiments with IgE and FcεRI. These SPR experiments suggest that the peptide inhibits the IgE:FcεRI interaction by binding to the high affinity receptor rather than to IgE.