Nontuberculous mycobacteria (NTM), including soil, water, and dust, are naturally present in the surroundings and can cause diseases, most particularly among immunosuppressed patients. NTM is primarily involved in respiratory disorders; people suffering from cystic fibrosis are more prone to NTM infections; and the most frequent isolates are Mycobacterium abscesses and Mycobacterium avium complex. Even if novel diagnostic techniques such as reverse hybridization assays and complete genome sequencing have been employed to recognize various NTM, treatment is still challenging, mainly due to the slow-growing nature of NTM, resistance to many antimicrobial agents, and the general unavailability of specific drugs. There are longer multidrug regimens essential for effective management, thus the need to develop enhanced diagnostic and treatment approaches. Therefore, this chapter briefly illustrate the epidemiology, pathogenesis, severity, and diagnosis, emphasizing challenges and precise treatment regimens for NTM.