Approximately 30% of the human genome, and likewise for other genomes, encodes membrane proteins. Also, the majority of known human pharmaceutical targets are membrane proteins. As a consequence, the future success of structure-based drug-design efforts will rely heavily on membrane-protein structural information. While a number of techniques are available to determine the structure of membrane proteins, crystallographic methods (either using two-dimensional or three-dimensional crystals) have been the most productive. Nonetheless, membrane-protein structure determination using crystallographic methods has encountered at least three serious bottlenecks: protein production, purification and crystallization. While a number of crystallization strategies for membrane proteins are available today, they all must ensure that the membrane protein of interest is thermodynamically stable for crystallization to be feasible. Thermodynamic stability is so fundamental to protein crystallization that it is often overlooked experimentally. Here, simple and effective protocols for determining the relative stabilities of membrane proteins using commercially available instruments and reagents are demonstrated. The results demonstrate suitability for the rapid screening of conditions that maximize protein stability using minimal amounts of reagents and protein.