Interstitial pneumonia in a transplant patient can have a varied etiology. Sirolimus (Rapamycin; Rapamune) is a popularly used immunosuppressant in solid organ transplantation that has anecdotally been associated with pulmonary toxicity. Sirolimus-induced pulmonary toxicity consists of a range of syndromes that is characterized by the presence of organizing pneumonia, interstitial pneumonitis, pulmonary alveolar proteinosis, focal fibrosis, or by the presence of alveolar hemorrhage. Diagnosis can be challenging and is usually made by exclusion of other etiologies. In this report we present two cases of sirolimus-associated pulmonary toxicity with a review of the literature.