Peptide purification on ever larger scale is a challenge for API manufacturers. Effective removal of commonly generated by-products during assembly and cleavage is essential (deletion peptides, Cis-Trans isomers of Pro, Succinimide from Asp, degradates of Trp generated by acid cleavage, Met-sulphoxide). Another indicator of the worthiness of stationary phases is the separation effectiveness of oligopeptides especially di-, tri-, penta-, and octapeptides. The major application is the final purification of recombinant human insulin from its highly similar analogs. Taking a systematic approach for phase screening for these purposes is essential. A simple step-wise guide is provided to choose the best matching stationary phase for any given purification challenges, because always the stationary phase should be chosen for the process and not the process optimized for the stationary phase.