The article discusses the advancements and challenges in the treatment of tuberculosis (TB) and nontuberculous mycobacterial (NTM) lung diseases. Over the past 20 years, TB drug discovery and development have seen significant progress, leading to improved understanding of mycobacterial biology and pharmacology. However, NTM lung diseases, caused by environmental mycobacteria, remain a neglected area with limited drug development pipelines. The authors highlight the similarities and differences between TB and NTM diseases, emphasizing the need to apply successful TB paradigms to NTM research. They discuss preclinical and clinical advances, including the use of repurposed antibiotics, re-engineered antibiotic classes, and novel chemical scaffolds. The article also explores the potential of targeted protein degradation as a new modality in anti-mycobacterial drug discovery. Despite the challenges, the authors argue that leveraging the well-supplied TB drug pipeline can help populate the thin NTM-PD pipeline, particularly through the use of compounds active against Mtb to validate targets in NTM.The article discusses the advancements and challenges in the treatment of tuberculosis (TB) and nontuberculous mycobacterial (NTM) lung diseases. Over the past 20 years, TB drug discovery and development have seen significant progress, leading to improved understanding of mycobacterial biology and pharmacology. However, NTM lung diseases, caused by environmental mycobacteria, remain a neglected area with limited drug development pipelines. The authors highlight the similarities and differences between TB and NTM diseases, emphasizing the need to apply successful TB paradigms to NTM research. They discuss preclinical and clinical advances, including the use of repurposed antibiotics, re-engineered antibiotic classes, and novel chemical scaffolds. The article also explores the potential of targeted protein degradation as a new modality in anti-mycobacterial drug discovery. Despite the challenges, the authors argue that leveraging the well-supplied TB drug pipeline can help populate the thin NTM-PD pipeline, particularly through the use of compounds active against Mtb to validate targets in NTM.