Have we realized the full potential of β-lactams for treating drug-resistant TB?

β-lactams are the most widely used antibiotics and are effective against a spectrum of pathogenic bacteria. Here, we focus on the state-of-the-art understanding of the molecular underpinnings that determine the overall efficacy of β-lactams against TB and include historical perspectives of this antibiotic class against this ancient disease. We summarize literature that describes why earlier generations of β-lactams are ineffective and the potential promise of newer β-lactams that exhibit improved efficacy against TB. Emerging evidence warrants renewed consideration of newer β-lactams in regimens for treatment of drug-resistant TB.