Urine is an extremely valuable sample type for biomarker discovery due to the non-invasive collection and the relatively low protein content, which makes detection of perturbations associated with disease easier. SELDI-TOF analysis is ideally suited for analysis of urine since the chromatographic capture mechanism can tolerate salt and urea in the urine sample that would otherwise need to be removed prior to mass spectrometric analysis. While neat urine can be analyzed directly on ProteinChip arrays, urine can also benefit from an enrichment step, which has been shown to increase the number of proteins detected more than twofold. Because urine volume and contents can vary substantially between individuals and within individuals over time, sample collection and storage should be carefully controlled to assure reproducible and clinically relevant results.