Diagnostic medicine has seen significant changes during the past decade. The emergence of proteomics and genomics has significantly increased our understanding of disease. These fields have also revealed the vast array of proteins that are expressed in various disease processes, such as cancer. Measurement of these unique proteins expressed in certain diseases may offer diagnostic clues or allow patient prognosis to be assessed. Another approach is to measure the effects that these ligands have on the structure and function of albumin. Albumin is known to play an important role in modulating the serum concentrations of various proteins produced by tumor cells. In this review, we introduce the reader to the technique of spin labeling followed by electron paramagnetic resonance spectroscopy. This method is a powerful tool for evaluating the structural and functional changes that can occur to albumin following the binding of various ligands. We describe the utility of this technique for the diagnosis of cancer and sepsis, as well as some other novel potential applications.