Statistical process control (SPC) is a robust set of tools that aids in the visualization, detection, and identification of assignable causes of variation in any process that creates products, services, or information. A tool has been developed termed Statistical Process Control in Proteomics (SProCoP) which implements aspects of SPC (e.g., control charts and Pareto analysis) into the Skyline software. It provides real time evaluation of the chromatographic performance (e.g., retention time reproducibility, peak asymmetry, and resolution); and mass spectrometric performance (targeted peptide ion intensity and mass measurement accuracy for high resolving power instruments) via control charts and boxplots. Its power as a quality control procedure lies in its emphasis on early detection of the LC MS/MS process performing outside experimentally-defined thresholds. SProCoP is compatible with both low resolution (i.e, SRM) and high resolution targeted MS/MS or MS1 filtering experiments.