In recent years, with the wide application of metagenomics next-generation sequencing, more and more rare pathogens have been detected in our clinical work, including non-tuberculous Mycobacterium, Corynebacterium, Fusarium, Cryptococcus pneumoniae, human herpes virus, torque teno virus, parvovirus, Tropheryma whipplei, Bartonella, Chlamydia psittaci, etc. It is difficult to determine whether these rare pathogens are clinically significant and need treatment. This article puts forward some suggestions and discussions on the diagnosis and treatment of pulmonary infections with some rare pathogens.