Our future research in this area will focus on developing better methods to fractionate cell extracts before mass spectrometry (MS). Defining the protein composition of a cell must also take into account the fact that mRNA splicing and covalent modifications generate protein isoforms that might contribute to important regulatory processes in the cell. Documenting the extent to which a protein is modified and the temporal changes in the modifications during disease can provide strategies for therapeutic intervention. Several approaches are being used to study post-translational modifications on a proteome-wide scale. Again, the most popular approach couples MS, which can detect even subtle covalent modifications, with methods to specifically enrich for modified proteins. Other strategies include the use of modification-specific antibodies. The techniques that catalog changes in gene expression, protein levels, or modification due to disease or other cellular perturbations are powerful methods of identifying potential targets for drug discovery. However, they do not reveal the biochemical mechanism of how a gene product is related to disease or whether the protein is likely to be amenable to drug development.