Tissue heterogeneity has always limited the information available from analysis of biological samples in the study of disease. Several approaches have been developed to address this problem, with laser capture microdissection (LCM) emerging as one of the methods of choice. LCM has been extensively used in combination with mutation detection studies and analyses of gene expression at the mRNA level and its potential in proteomics-based research is beginning to be realised. Here we review the progress made to date in the analysis of proteins in LCM-captured material and evaluate the scope and limitations of this approach.