Acute myeloid leukaemia (AML) is a genetically heterogeneous haematopoietic neoplasm characterised by the accumulation of transformed immature blood progenitors in bone marrow. Since 1973, the backbone treatment has relied on the combination of cytarabine and an anthracycline, followed by allogeneic haematopoietic transplant if eligible. Therefore, the treatment decisions have largely revolved around chemotherapy drug intensity. Despite advances in our understanding of the underlying biology over the past decades, AML remains a therapeutic challenge as the overall survival is poor and treatment options are limited for relapsed/refractory AML or for unfit patients. After four decades without substantial changes, eight new noncytostatic drugs have been granted approval: vyxeos, enasidenib, gilteritinib, glasdegib, gemtuzumab ozogamicin, ivosidenib, midostaurin, and venetoclax. Despite promising preliminary results, some indications are based on early efficacy data, obtained in single-arm nonrandomised trials, highlighting the necessity for further validation in extended clinical trials. Interestingly, several druggable targets have been identified recently, associated with specific target-directed drugs. Based on the preclinical data available, great impact on clinical outcomes for patients with AML is expected, potentially increasing the therapeutic landscape for this disease.