The green fluorescent protein (GFP) of Aequorea victoria has become a convenient and versatile tool as a reporter protein in molecular cell biology and developmental biology. Here, it is shown that GFP may advantageously be used as a reporter system for bioprocess monitoring as well. Examples are given for monitoring fermentation as well as downstream processes for protein recovery. Thus, separation processes based on the application of affinity-fusion tags may be optimized in terms of the operational conditions by using GFP as a model target protein owing to facile screening by simple visual inspection. This item is discussed together with the presentation of a novel fusion tag with strong affinity for metal–chelate ligands: hisactophilin, a histidine-rich protein of Dictyostelium discoideum. This tag is of particular interest for affinity separation processes requiring multiple sites of interaction like aqueous and reverse micellar two-phase extraction as well as precipitation.