Tuberculosis (TB) drug discovery and development have undergone a major transformation over the past 20 years, with successful public-private partnerships and sustained funding leading to a better understanding of mycobacterial disease biology and a robust drug development pipeline. Preclinical and clinical development has evolved from traditional concepts to adaptive designs that allow rapid evaluation of regimens that could shorten treatment duration. However, nontuberculous mycobacterial (NTM) lung disease, a fatal and difficult-to-treat condition, has seen little progress in drug development, with a nearly empty pipeline. This review discusses the similarities and differences between TB and NTM lung diseases, compares preclinical and clinical advances, and identifies major knowledge gaps and areas of cross-fertilization. It argues that applying successful paradigms from TB research to NTM could help populate the NTM pipeline and accelerate curative regimen development. TB is caused by Mycobacterium tuberculosis (Mtb) and is characterized by immune cell aggregates called granulomas. Treatment involves four drugs taken daily for 2 months, followed by a continuation phase. Multidrug resistance (MDR) and extensively drug-resistant (XDR) TB complicate treatment. NTM-PD, caused by environmental mycobacteria, is more challenging to treat, often requiring long-term antibiotic therapy with multiple drugs. NTM-PD is not always reportable, leading to underestimation of its prevalence. NTM species are intrinsically resistant to many drug classes, and their treatment is complicated by factors such as biofilm formation and drug resistance. TB and NTM share key shortcomings in treatment, including high pill burden, long duration, poor cure rates, toxicity, and drug interactions. However, NTM-PD is more difficult to cure due to factors such as intrinsic resistance, biofilm formation, and immune deficiency. The treatment of TB and NTM lung diseases shares similar challenges, and the development of shorter, more effective regimens is a priority. Repurposing antibiotics has shown promise in TB treatment, with drugs like moxifloxacin and linezolid being effective. However, their use in NTM-PD is limited due to intrinsic resistance and other factors. New drug classes, such as re-engineered oxazolidinones, are being developed to improve tolerability and efficacy. Rifamycins, despite their high conservation in Mtb, are less active against NTM species due to intrinsic resistance mechanisms. Phenotypic screening and target deconvolution have led to the identification of novel drug targets, such as cell wall biosynthesis pathways and respiratory chain components. These approaches have provided new avenues for TB drug discovery and could be applied to NTM-PD. Targeted protein degradation (TPD) is a new modality in anti-mycobacterial drug discovery, with PROTACs showing potential for degrading bacterial proteins. Preclinical models of TB and NTM infection are essential for evaluating drug efficacyTuberculosis (TB) drug discovery and development have undergone a major transformation over the past 20 years, with successful public-private partnerships and sustained funding leading to a better understanding of mycobacterial disease biology and a robust drug development pipeline. Preclinical and clinical development has evolved from traditional concepts to adaptive designs that allow rapid evaluation of regimens that could shorten treatment duration. However, nontuberculous mycobacterial (NTM) lung disease, a fatal and difficult-to-treat condition, has seen little progress in drug development, with a nearly empty pipeline. This review discusses the similarities and differences between TB and NTM lung diseases, compares preclinical and clinical advances, and identifies major knowledge gaps and areas of cross-fertilization. It argues that applying successful paradigms from TB research to NTM could help populate the NTM pipeline and accelerate curative regimen development. TB is caused by Mycobacterium tuberculosis (Mtb) and is characterized by immune cell aggregates called granulomas. Treatment involves four drugs taken daily for 2 months, followed by a continuation phase. Multidrug resistance (MDR) and extensively drug-resistant (XDR) TB complicate treatment. NTM-PD, caused by environmental mycobacteria, is more challenging to treat, often requiring long-term antibiotic therapy with multiple drugs. NTM-PD is not always reportable, leading to underestimation of its prevalence. NTM species are intrinsically resistant to many drug classes, and their treatment is complicated by factors such as biofilm formation and drug resistance. TB and NTM share key shortcomings in treatment, including high pill burden, long duration, poor cure rates, toxicity, and drug interactions. However, NTM-PD is more difficult to cure due to factors such as intrinsic resistance, biofilm formation, and immune deficiency. The treatment of TB and NTM lung diseases shares similar challenges, and the development of shorter, more effective regimens is a priority. Repurposing antibiotics has shown promise in TB treatment, with drugs like moxifloxacin and linezolid being effective. However, their use in NTM-PD is limited due to intrinsic resistance and other factors. New drug classes, such as re-engineered oxazolidinones, are being developed to improve tolerability and efficacy. Rifamycins, despite their high conservation in Mtb, are less active against NTM species due to intrinsic resistance mechanisms. Phenotypic screening and target deconvolution have led to the identification of novel drug targets, such as cell wall biosynthesis pathways and respiratory chain components. These approaches have provided new avenues for TB drug discovery and could be applied to NTM-PD. Targeted protein degradation (TPD) is a new modality in anti-mycobacterial drug discovery, with PROTACs showing potential for degrading bacterial proteins. Preclinical models of TB and NTM infection are essential for evaluating drug efficacy