Fast and precise heating by microwave irradiation during solid-phase peptide synthesis (SPPS) can reduce reaction times as well as provide better purities and greater yields for the synthesis of difficult peptides. Microwave- assisted SPPS has proven to be a useful and reliable tool for the synthesis of peptides as well as small proteins. It is particularly well suited for sequences with a high propensity to form β-sheet-type structures and for sterically difficult couplings. In this protocol, conditions and detailed procedures are described for performing microwave-assisted SPPS using the Syro Wave ?. Here we describe the synthesis of two difficult peptide sequences: the first is derived from the C-terminus of the MuLV CTL epitope, the second is a de novo designed peptide with a C-terminal alkyne.