Lung transplantation is an important therapy for end-stage respiratory failure in patients who have exhausted other therapeutic options. The lung is unique among solid-organ transplants in that it is exposed to the outside environment, and undergoes continuous stimulation from infectious and non-infectious agents, which may play a part in upregulating the immune response to the allograft. Despite induction immunosuppression and the use of aggressive maintenance regimens, acute allograft rejection is still a major problem, especially in the first year after transplant, with important diagnostic and therapeutic challenges. As well as being responsible for early graft failure and death, acute rejection also initiates alloimmune responses that predispose patients to chronic lung allograft dysfunction, in particular bronchiolitis obliterans syndrome. Cellular responses to human leukocyte antigens (HLAs) on the allograft have traditionally been considered the main mechanism of acute rejection, although the influence of humoral immunity is increasingly recognised. Here, we present two cases of acute cellular rejection (ACR) in the early post-transplant period and review the pathophysiology, diagnosis, clinical presentation and treatment of ACR.