Although great progress has been made in the understanding and treatment of acute leukemia, this disease has not been conquered. For emergency providers (EPs), the presentation of these patients to an emergency department presents a host of challenges. A patient may present with a new diagnosis of leukemia or with complications of the disease process or associated chemotherapy. It is incumbent on EPs to be familiar with the manifestations of leukemia in its various stages and maintain some suspicion for this diagnosis, given the nebulous and insidious manner in which leukemia can present.