Abstract β-Lactamase has emerged as the heir apparent to β-galactosidase as a catalytic reporter for imaging biological events in live mammalian cells. In recent years, several publications have demonstrated the advantages of β-lactamase as a reporter in applications ranging from monitoring of gene transcription to detection of protein–protein interactions. Now, Rao et al. have demonstrated that β-lactamase can also serve as a sensitive fluorogenic reporter for imaging Tetrahymena ribozyme activity in live cells. This assay should pave the way for the screening of large libraries of ribozyme mutants by flow cytometry and, therefore, the isolation of variants with improved splicing activity in the cytoplasm of mammalian cells.