Recently, biobehavioral nursing scientists have focused their attention on the search for biomarkers or biological signatures to identify patients at risk for various health problems and poor disease outcomes. In response to the national impetus for biomarker discovery, the measurement of biological fluids and tissues has become increasingly sophisticated. Urine proteomics, in particular, may hold great promise for biobehavioral focused nursing scientists for examination of symptom-and syndrome-related research questions. Urine proteins are easily accessible secreted proteins that provide direct and indirect windows into bodily functions. Advances in proteomics and biomarker discovery provide new opportunities to conduct research studies with banked and fresh urine to benefit diagnosis, prognosis, and evaluation of outcomes in various disease populations. This article provides a review of proteomics and a rationale for utilizing urine proteomics in biobehavioral research. It addresses as well some of the challenges involved in data collection and sample preparation.