There is no means for directly quantifying the purity of a protein sample. Demonstration of purity of a protein preparation always involves an assessment of the quantity of particular types of impurities, or simply demonstrating their absence. Whether the goal is interpretation of analytical data, demonstration of the quality of a process, or assuring safety of a biopharmaceutical product, determination of sample purity is of central importance. This chapter will focus primarily on methods for detecting protein impurities in protein samples and will describe methods, their capabilities, and their limitations.