Translation plays a key role in the survival of any cell and is a hub for many regulatory pathways that control cellular growth. Due to this complexity, the ribosome has proven to be a vulnerable antibiotic target and several existing antituberculous compounds block translation. We have capitalized on recent advances in cryo-EM techniques to explore the unique structural aspects of the mycobacterial ribosome that might alter antimicrobial efficacy and be exploited by new therapeutics.