Alzheimer’s disease (AD) is a neurodegeneration disease with severe cognition disorder, which is more prevalent in the elderly people. There are currently no specific drugs for AD in the world. At present, the drugs for clinical treatment of AD are mainly drugs that improve cognitive symptoms (such as cholinesterase inhibitors (donepezil, rivastigmine)) and control psycho-behavioral symptoms (such as 5-hydroxytryptamines). Unfortunately, these drugs only alleviate some of the clinical symptoms and do not prevent or reverse the progression of AD pathology. Amyloid β (Aβ) formation is one of the typical pathological features of AD, which plays an important role in the development of AD. Different forms of Aβ including monomers, oligomers, fibrils, and senile plaques may play different roles in the development of AD. Based on a main pathological molecule of Aβ in AD, the amyloid cascade hypothesis was proposed and widely recognized by the academia. However, current therapies targeting Aβ either secretase inhibitors (e.g. Verubecestat, Semagacestat) or immunotherapies (e.g. AN1792, Crenezumab) in clinical trials have failed. There are many problems in the process of clinical trials. Firstly, AD animal models are diversified, but their applicability and practicability are still controversial. Secondly, the lack of convenient and effective biomarkers in the clinical diagnosis of AD that leads to unsatisfactory selection of the subjects. Thirdly, the investigational drugs have potential safety risks in patients and the treatment period is short. Therefore, the failure of clinical trials targeting Aβ suggests that the experimental design needs to be more rigorous and the role of Aβ in the disease needs to be reexamined. In addition, other factors including Tau hyperphosphorylation, neuroinflammation, oxidative stress together with Aβ participate in the progression of AD, meaning the amyloid cascade hypothesis may be no longer sufficient to comprehensively summarize the symptoms and pathogenesis of AD, hence the combination of multiple factors influence the pathogenesis of AD should be pay more attention. This article reviews the formulation and development of amyloid cascade hypothesis, the role of Aβ in AD progression and the therapeutic effect of the treatment targeting Aβ. We are hoping to provide a comprehensive overview of Aβ for understanding the pathological mechanism of AD, which may be useful in diagnosing and treating AD.