Advances in genomics and immunology are revolutionizing our understanding and treatment of cancer with improved treatment outcomes and patient quality of life. With the increasing use of immunotherapy and molecular targeted therapy, a variety of unusual and/or opportunistic infections are also observed. A variety of factors including use of immunosuppression for immune-mediated adverse effects play an important role for increasing the likelihood of these infections and form the basis of this case-based review. Imaging features of infections arising in patients undergoing immunotherapy regimens have not been previously highlighted. Prompt recognition of the spectrum of mycobacterial, bacterial, invasive fungal and viral pathogens can potentially lead to reduction in the high morbidity and mortality in this patient population.