Complement C5 is cleaved by proteolysis in the terminal phase of complement activation generating the pro-inflammatory C5a and membrane attack complex nucleator C5b. Whereas purification of its paralogues C3 and C4 from plasma is relatively straightforward, C5 purification is more complicated due to the lower amounts present and overlaps with the much more abundant C3 during several chromatographic steps. Here we describe our procedure for purifying homogenous, monodisperse, and crystallizable C5.