Protein synthesis is a major target within the bacterial cell for antibiotics (1,2). Investigations into ribosome-targeting antibiotics have provided much needed functional and structural insight into their mechanism of action (1,2). However, the increasing prevalence of multi-drug-resistant bacteria has limited the utility of our current arsenal of clinically relevant antibiotics, highlighting the need for the development of new classes (3,4). In this presentation, I will discuss our recent structural insights into the mechanism of action of novel ribosome-targeting compounds as well as novel molecular mechanisms of bacterial resistance, with an outlook as to how this information could be used for the development of improved drugs that inhibit bacterial protein synthesis (3,4).