Membrane proteins represent roughly one-third of the proteins encoded in the genome, yet fewer than 1% of the proteins of known structure. High-throughput crystallography offers the hope of correcting this imbalance. In order for large-scale membrane protein structural biology to realize its full promise, however, significant technical challenges must be overcome, the two most substantial being facile protein overexpression and reliable methods for crystal growth. (C) 2003 Elsevier Science (USA). All rights reserved.