The release of the sequence of the human genome in early 2000 generated enormous excitement with the promise of rapid identification of the gene products responsible for cellular function. What has become apparent is that knowledge of the DNA sequence of the gene that is involved in a particular metabolic process is insufficient to predict its function, expression and activity. The very numbers illustrate this difference – it is estimated that there are 22,000 to 25,000 known genes in the human genome but there are probably greater than 1,000,000 proteins in the human proteome. This discrepancy has extended the focus of proteomics to the analysis and understanding of the modifications that occur to proteins both during and after translation of the gene. As we move further into understanding protein function it is becoming increasingly obvious that many of the changes associated with disease and differentiation are to do with the modifications to the proteins rather than only to do with the regulation of the expression of the gene. The main difficulty which has slowed the understanding of the biological role of these protein modifications has been the perception that the analysis of these alterations is difficult and is best left to the limited number of experts in each field. However, the reality is that the increasing availability of sample preparation, mass spectrometric and bioinformatic tools specifically designed for the analysis of post-translational modifications, is enabling the function of these instruments of biological diversity to be explored.