Acute myeloid leukemia (AML) is driven by complex mutations and cytogenetic abnormalities with profound tumoral heterogeneity, making it challenging to treat. Ten years ago, the 5-year survival rate of patients with AML was only 29% with conventional chemotherapy and stem cell transplantation. All attempts to improve conventional therapy over the previous 40 years had failed. Now, new genomic, immunological, and molecular insights have led to a renaissance in AML therapy. Improvements to standard chemotherapy and a wave of new targeted therapies have been developed. However, how best to incorporate these advances into frontline therapy and sequence them in relapse is not firmly established. In this review, we highlight current treatments of AML, targeted agents, and pioneering attempts to synthesize these developments into a rational standard of care (SoC).