Lerner's research into catalytic antibodies provided a method of catalyzing chemical reactions thought impossible using classical techniques. He was one of the pioneers in developing the field of combinatorial libraries, and in 1992, together with Sydney Brenner, he published a sentinel paper launching the field of DNA-encoded libraries. In addition, Lerner has led extensive studies into protein structure, characterised cis-9,10-octadecenoamide, a novel lipid hormone that induces sleep, and provided the first evidence of a role for ozone in human disease. In 1967 Lerner discovered the role of anti-GBM antibodies in the pathogenesis of Goodpasture's disease. As of 2007, Lerner's résumé listed 67 patents and 403 published scientific papers.