In biological materials such as cellular extracts and physiological fluids, glycoproteins are often encountered in minute quantities, placing high demands on both the measurement sensitivity and proper isolation procedures. A combination of orthogonal separation techniques and the use of affinity principles are the most commonly practiced isolation/enrichment strategies. Glycoproteins of interest may be encountered as either soluble or membrane-bound molecules. The isolation strategies will vary, depending upon whether such glycoproteins occur in cytosolic space, nucleus, extracellular space, cellular, or subcellular membranes. Also, any isolation protocol has to be adjusted to take into account the physicochemical properties of a given glycoprotein or a glycoprotein class. The methods used in any glycoprotein isolation and enrichment protocols are very dependent on whether or not a biological activity must be retained for further studies. Generally, glycoproteins can be purified by most conventional protein separation methodologies, including gel electrophoresis and various chromatographic forms such as ion-exchange, size exclusion, reversed phase using C18, C8, or C4 columns, hydrophobic interaction, and affinity. A most useful, specific isolation principle is currently the use of lectins that are immobilized on chromatographic resins.