The solid phase peptide synthesis is based on repetitive cycles (deprotection and coupling) that cannot be monitored with the analytical methods used in organic chemistry because of the presence of the solid support. Various methods have been developed for monitoring the synthetic steps, which can be qualitative and/or quantitative destructive or non-destructive. The irreversible or destructive analytical methods are carried out on aliquots of the peptide-resin and a lot of these are based on the presence of the free amino group. The nondestructive methods can be carried out on the total batch; many of these derive from the modification of the techniques used in organic chemistry such as UV, IR and NMR. If the peptide is cleaved from the resin, it is possible to utilize the conventional analytical methods used for organic chemistry. Every detection method differs in terms of sensitivity, applicability, rapidity and almost all cannot be applied in the automated instrumentations.