Acute humoral rejection (AHR) should be considered in patients with renal allograft dysfunction that develops at any stage of the post-transplant course. AHR has become increasingly recognized and is now more accurately diagnosed by the use of flow cytometry cross-matching, the identification of C4d deposits shown on renal allograft biopsy, and the assessment of allograft function. Although plasma exchange has been a popular treatment for AHR, other treatment modalities have also been used by transplant centers. We present case reports of two patients whose AHR was diagnosed and treated at our medical center.