The complement system is a key component of the innate immune response and contributes to protection against infection and recovery from injury. Key components of the complement system are the anaphylatoxins C3a and C5a, which acts via there receptors, C3aR (C3a) and C5aR1 and C5aR2 (C5a), to modulate a range of inflammatory responses. However, aberrant regulation of this system is implicated in a broad range of inflammatory-based diseases including many neurodegenerative conditions. A number of small peptide-based agonists and antagonists of the complement receptors, primarily based on the C-terminus of C3a and C5a, have previously been developed, but ligands with improved selectivity, pharmacokinetic and pharmacodynamic profiles, are desirable. In this presentation, I will describe the design and characterisation of next-generation complement peptide ligands that address some of the limitations of the currently available molecules both as valuable tools for further elucidating the physiological role of C3aR, C5aR1, and C5aR2, and as potential drug leads.