Over the last decade, tandem mass tag (TMT) technology has grown to become one of the predominant methods for global protein quantitation. Advancements in isobaric tag reagent chemistry, instrument hardware and data analysis software over the years have helped expand the level of proteomic sample multiplexing from 6 to 18 samples. This seminar will highlight advances in sample preparation necessary to prepare high quality peptide samples for isobaric tag labeling. Additionally, this seminar will provide an overview of methods for improving proteomics sample preparation reproducibility and depth of coverage depth for different sample types and limited sample amounts.