Protein folding is a fundamental process of life with important implications throughout biology. Elaborate mechanisms exist to regulate and assist folding. Moreover, tens of thousands of mutations have now been associated with diseases and it is thought that most of these mutations affect protein folding and trafficking rather than function. Consequently, there has been an enormous effort over the years to understand how proteins fold. Essentially all of the effort has been directed at soluble proteins, however, and membrane proteins have been largely shunted aside. The lack of effort has not occurred because membrane proteins are unimportant or uninteresting, but because of the great technical challenges they present. It is a challenge that we must overcome if we ever hope to understand membrane biology and disease mechanisms involving a large fraction of the protein universe. We are working to understand folding mechanisms and to develop techniques to study folding and expand the field.