Curl's later research interests involved physical chemistry, developing DNA genotyping and sequencing instrumentation, and creating photoacoustic sensors for trace gases using quantum cascade lasers. He is known in the residential college life at Rice University for being the first master of Lovett College.
Curl retired in 2008 at the age of 74, becoming a University Professor Emeritus, Pitzer-Schlumberger Professor of Natural Sciences Emeritus, and Professor of Chemistry Emeritus at Rice University.