Nontuberculous mycobacteria (NTM) are important environmental pathogens that can cause a broad spectrum of diseases. The last few years brought several changes in this expanding field: The number of infections that can be associated with specific species as well as the number of new species as etiological agents has exploded due to the development of new diagnostic tools. The incidence of disseminated Mycobacterium avium complex (MAC) infections in HIV patients is decreasing with more potent anti-HIV treatments, while the rate of pulmonary NTM infection and disease as well as the prevalence of Buruli ulcer, a chronic, necrotizing, progressive ulcerous disease caused by Mycobacterium ulcerans, is increasing. The disease manifestations depend on the interaction between the specific mycobacterial pathogen and the host’s immune system. This article presents an update of the epidemiology, diagnosis, and treatment of NTM-associated pulmonary disease, lymphadenitis, skin and soft tissue disease, skeletal infection and foreign body- and catheter-related NTM infections.