Despite the tremendous progress made in the comprehension of acute myeloid leukemia (AML) over the last 30 years most patients die from their disease. Our understanding of AML has relied on an intensive in-vitro research approach, based on AML cell lines as well as primary AML patient cells. However, experimental insight into the early events of AML leukemogenesis before they become clinically observable is not possible in humans. Thus, preclinical animal models have served the purpose to extend our knowledge of the disease as well as to develop innovative therapeutic strategies. Today, xenograft models using patient-derived neoplastic/leukemia cells represent the strategy of choice for preclinical studies of AML. These models exhibit several key advantages over AML cell lines. In fact, patient-derived cells, in contrast to AML cell lines, encompass the entire complexity of AML disease and can therefore provide more trustworthy results on the efficacy outcome of novel therapies. One other important aspect in the development of xenograft models of AML is the possibility to use imaging techniques to monitor in-vivo the progression of the disease. Imaging techniques also authorize the evaluation of the efficacy of an experimental treatment on tumor growth. This review will focus on the description of xenograft models of AML and will provide researchers and clinicians an overview of how these models have been used for the development of new therapeutic options and new imaging approaches to study AML in-vivo.