Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults in the United States, with approximately 19,520 new cases estimated for 2018. Despite advances in the management of hematologic malignancies, the development of novel targeted and immune therapies, and improvements in supportive care, the overall outcome for patients with AML remains poor due to several factors, including increased frequency in the older population, poor response to chemotherapy, high relapse rates, and limited effective therapy options in relapsed patients. In addition, AML presents a substantial clinical and financial burden attributable in part to the heterogenic characteristics at presentation, such as varied age distributions and cytogenetic and molecular abnormalities, coupled with prolonged hospitalizations, high rates of infectious complications, and need for allogeneic stem cell transplants. Several unmet needs exist in AML. For instance, more-effective, less-toxic treatments are urgently needed because many patients with AML are not candidates for standard induction therapy. AML is also characterized by high rates of relapsed/refractory disease; therefore, strategies to reduce relapse are important. Other unmet needs center on poor quality of life from disease- and therapy-related toxicities and inadequate psychosocial support frequently experienced by many patients with AML and by their caregivers. This review will discuss these issues and additional challenges faced both by patients with AML and by caregivers and medical personnel who work in the AML setting.