Rhodococcus equi is an aerobic coccobacillus that causes bronchopneumonia in livestock. Most human infections with R. equi occur among immunocompromised population, especially patients with human immunodeficiency virus infection and cancer. We looked at the unique presentation and management of R. equi infections in patients with cancer from our own experiences and from a review of the literature. Rhodococcus equi presents most commonly in immunocompromised patients as a pulmonary disease. In addition, more than 80% of immunocompromised patients develop bacteremia compared with 30% of immunocompetent patients. Because Rhodococcus is a known pathogen of livestock, it is not surprising that approximately 25% to 45% of infected patients with cancer are exposed to farm animals. Rhodococcus equi infections in patients with cancer are rare but may be life threatening if not recognized and treated promptly. Antibiotic resistance and the frequent propensity of R. equi infections to recur require the use of combination antibiotic therapy for a prolonged period.