Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the main cause of dementia worldwide. It affects cognitive decline, functional impairment and a significant burden on society. For many years, available treatments focussed on reducing symptoms yet also altered the underlying neurodegenerative process. Recent advances in drug development show that there are real possibilities for disease-modifying therapies that will target pathomechanisms such as amyloid-β deposition. This review presents the current knowledge about donanemab, a humanized monoclonal antibody that target N-terminal pyroglutamate-modified amyloid-β, focussing on its mechanism of action, pharmacokinetics, clinical efficacy and safety profile. The review was based on published results of clinical trials and review articles identified in medical databases. Donanemab promotes microglia-mediated clearance of amyloid plaques by binding to dense-core amyloid plaques. Additionally, it reduces plasma concentrations of phosphorylated tau 217 and glial fibrillary acidic protein. Pharmacokinetic studies show predictable, dose-dependent exposure after intravenous administration. In phase II and III clinical trials, donanemab treatment resulted in a significant reduction in cognitive and functional decline. Positron emission tomography imaging showed substantial amyloid reduction and changes in plasma and cerebrospinal fluid biomarker levels. The most common adverse event was amyloid-related imaging abnormalities, but most cases were asymptomatic and resolved after adjusting treatment. Compared with other anti-amyloid monoclonal antibodies, donanemab achieves more rapid and complete amyloid clearance than aducanumab and shows similar disease-modifying activity to lecanemab. Ongoing research on emerging therapies for AD may lead to further breakthroughs in disease treatment.