A review is presented regarding the limitations, problems, shortcomings and pitfalls of identifying protein by use of mass spectrometry. These troubles are seen on the laboratory in the proteomics area at different levels, instrumental and data mining. There are three factors that are considered to affect these problems. The limited experience of some investigators, the poor bioinformatic know-how and the low abundance of proteins. This review further provides information on the reliability of PrI and the validation of the identification process for MS users. Lastly, this review prevents false accumulation of PrI in the literature and databases.