Antimicrobial resistance is on the rise and very few new antibiotics are being discovered. Some alternative approaches for antibiotic discovery in order to combat the threat of antimicrobial resistance have been discussed. These include drug repurposing, antivirulence approaches, inhibition of quorum sensing, inhibition of biofilms, bacterial toxin neutralization, metal ion chelation, antibiotics from plants, nanoparticles as antibiotics, and antibiotics against persister bacteria. Methods for improved drug delivery targeting infected sites and intracellular bacteria are also discussed.