Janet Smith's research focuses on understanding biological processes through knowledge of the structures of key protein molecules. She has made major contributions to the understanding of catalysis and regulation in glutamine amidotransferases and phosphoribosyltransferases by solving and interpreting crystal structures of several enzymes of each type. She has solved crystal structures of photosynthetic proteins, leading to a new understanding of their function. She has also contributed to the development of methods for rapid determination of protein crystal structures, particularly using synchrotron X-ray sources.