Nontuberculous mycobacteria (NTM) are ubiquitous, opportunistic microorganisms found primarily in soil and water. The most common form of disease they cause is the pulmonary form (nontuberculous mycobacterial pulmonary disease, NTM-PD), and most important specimens for evaluation are respiratory specimens (sputum, lavages, or lung tissue biopsies). Thus, this paper examines the clinical importance of nontuberculous mycobacteria isolated from respiratory samples. Globally, there is an increase in isolation and incidence of NTM and, consequently, the prevalence of NTM-PD. One of the possible reasons is the aging of the population with increasing number of comorbidities and a decline in immunity, a trend that is present in all countries, especially developed ones. From the latest guidelines of ATS/ERS/ESCMID/IDSA societies, the species that globally present a threat are Mycobacterium avium complex (MAC), M. kansasii, M. xenopi from slow-growing and M. abscessus from rapid-growing NTMs. Also, many local researches show results that are different depending on the part of the world in which they were conducted. Furthermore, it was found that the frequency of NTM isolation and NTM-PD depends on the geographical location. In Croatia, several studies have been conducted in this area. From them, we know that the isolation frequency of NTM and NTM-PD is rising, and that most clinically significant species are M. xenopi, M. kansasii, M. abscessus and MAC. Also, it was shown that the burden of NTM isolation and NTM-PD differs in the continental part of the country, compared to the coastal part. Finally, awareness and knowledge of clinical importance is important when making a definitive diagnosis of NTM-PD and deciding on optimal treatment regimen.