This chapter provides an introduction to and an overview of current instrumentation for solid-phase peptide synthesis (SPPS). Presently, the two most common designs differ in their mode of liquid handling: the first relies on valves and valve blocks for distribution of reagents, while the second uses a robotic platform. They also differ in their mode of mixing the reactants in the reaction vessel, where the former can utilize sparging, 180� rotational shaking, or vortexing, while the latter typically uses vortexing. Valve-based instruments are often single channel (one peptide at a time), but can also be expanded to allow parallel synthesis of up to 12 and even 24 peptides, however, at the price of added complexity. Valve systems often use inert gas for their operation. The X–Y robotic platforms are ideal for parallel synthesis of large numbers of peptides up to 192 and even peptide libraries. However, although less common, the robotic platform is also very suitable for single-channel operation and can also be used for operations under inert gas. Some single-channeled synthesizers are available with UV feedback monitoring of the Fmoc removal which can be useful for some applications. Importantly, single-channel synthesizers can be equipped with fast and precise microwave heating to accelerate the synthesis and to overcome synthetic difficulties. A whole range of synthesizers with different designs are commercially available. The choice of peptide synthesizer will depend on intended application, for example on the type of chemistry, scale, and the number of peptides that are required and so on.