β-lactam antibiotics are one of the most commonly used drugs for treating bacterial infections, but their clinical effectiveness has been severely affected with bacteria developing resistance against their action. Production of β-lactamase enzymes by bacteria that can degrade β-lactams is the most common mechanism of acquiring such resistance, leading to the emergence of multiple-drug resistance in them. Therefore, the development of efficient approaches to combat infections caused by β-lactamase producing and multidrug-resistant bacteria is the need of the hour. The present review attempts to understand such recent strategies that are in line for development as potential alternatives to conventional antibiotics. We find that apart from efforts being made to develop new antibiotics, several other approaches are being explored, which can help tackle infections caused by resistant bacteria. This includes the development of plant-based drugs, antimicrobial peptides, nano-formulations, bacteriophage therapy, use of CRISPR-Cas9, RNA silencing and antibiotic conjugates with nanoparticles of antimicrobial peptides. The mechanism of action of these novel approaches and potential issues limiting their translation from laboratory to clinics is also discussed. The review is important from an interesting knowledge base which can be useful for researchers working in this domain.