Since the 1940s beta-lactam antibiotics have been used to treat bacterial infections. However, emergence and dissemination of beta-lactam resistance has reached the point where many marketed beta-lactams no longer are clinically effective. The increasing prevalence of multidrug-resistant bacteria and the progressive withdrawal of pharmaceutical companies from antibiotic research have evoked a strong reaction from health authorities, who have implemented initiatives to encourage the discovery of new antibacterials. Despite this gloomy scenario, several novel beta-lactam antibiotics and beta-lactamase inhibitors have recently progressed into clinical trials, and many more such compounds are being investigated. Here we seek to provide highlights of recent developments relating to the discovery of novel beta-lactam antibiotics and beta-lactamase inhibitors.