Seemingly innocuous nontuberculous mycobacteria (NTM) species, classified by their slow or rapid growth rates, can cause a wide range of illnesses, from skin ulceration to severe pulmonary and disseminated disease. Despite their worldwide prevalence and significant disease burden, NTM do not garner the same financial or research focus as Mycobacterium tuberculosis. In this review, we outline the most abundant of over 170 NTM species and inadequacies of diagnostics and treatments and weigh the advantages and disadvantages of currently available in vivo animal models of NTM. In order to effectively combat this group of mycobacteria, more research focused on appropriate animal models of infection, screening of chemotherapeutic compounds, and development of anti-NTM vaccines and diagnostics is urgently needed.