Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder characterized by the failure of cerebral neurons and the disability of affected individuals in performing normal daily activities. The exact cause of AD remains unknown, leading to the emergence of several hypotheses and therapeutic targets, including acetylcholinesterase, cholinergic receptors, N-methyl-D-aspartate receptors, phosphodiesterase, amyloid β protein, protein phosphatase 2A, glycogen synthase kinase-3 beta, β-secretase, γ-secretase, α-secretase, serotonergic receptors, glutaminyl cyclase, tumor necrosis factor-α, and γ-aminobutyric acid receptors. Despite extensive research and clinical trials, only a few drugs have been approved for AD treatment, such as galantamine, donepezil, rivastigmine (ChEIs), memantine (NMDA antagonist), and aducanumab and lecanemab (selective anti-Aβ monoclonal antibodies). Many other drugs have failed in clinical trials, raising questions about the significance of certain therapeutic targets. However, some promising data from other drugs suggest that their targets may be crucial for developing more effective anti-Alzheimer drugs. The etiology of AD is still incompletely understood, with genetic and environmental factors playing significant roles. Hypotheses include the cholinergic hypothesis, amyloid cascade hypothesis, tau hypothesis, mitochondrial cascade hypothesis, oxidative stress hypothesis, excitotoxicity hypothesis, and neuroinflammation hypothesis. Each hypothesis has led to the development of various drugs, but clinical trial results have questioned the significance of these hypotheses. For instance, the amyloid hypothesis has been challenged by repeated failures in Aβ-targeted clinical trials, while the tau hypothesis suggests that tau pathology may be more critical than amyloid plaques. Several challenges exist in AD treatment, including the lack of evidence for the exact mechanism and primary target, the absence of neuronal protective or regenerative drugs, and the complexity of the disease. AD is a chronic and progressive disease, requiring long-term drug safety and specific studies for each stage. Despite these challenges, there have been advances in anti-Alzheimer drugs and their mechanisms of action. Cholinergic drugs, glutamatergic drugs, phosphodiesterase inhibitors, anti-Aβ drugs, tau protein targeting drugs, and β-secretase acting drugs have shown potential in clinical trials. However, many drugs have failed due to toxicity, cognitive worsening, and lack of efficacy. The development of new drugs that target specific therapeutic targets while avoiding adverse effects remains a critical area of research.Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder characterized by the failure of cerebral neurons and the disability of affected individuals in performing normal daily activities. The exact cause of AD remains unknown, leading to the emergence of several hypotheses and therapeutic targets, including acetylcholinesterase, cholinergic receptors, N-methyl-D-aspartate receptors, phosphodiesterase, amyloid β protein, protein phosphatase 2A, glycogen synthase kinase-3 beta, β-secretase, γ-secretase, α-secretase, serotonergic receptors, glutaminyl cyclase, tumor necrosis factor-α, and γ-aminobutyric acid receptors. Despite extensive research and clinical trials, only a few drugs have been approved for AD treatment, such as galantamine, donepezil, rivastigmine (ChEIs), memantine (NMDA antagonist), and aducanumab and lecanemab (selective anti-Aβ monoclonal antibodies). Many other drugs have failed in clinical trials, raising questions about the significance of certain therapeutic targets. However, some promising data from other drugs suggest that their targets may be crucial for developing more effective anti-Alzheimer drugs. The etiology of AD is still incompletely understood, with genetic and environmental factors playing significant roles. Hypotheses include the cholinergic hypothesis, amyloid cascade hypothesis, tau hypothesis, mitochondrial cascade hypothesis, oxidative stress hypothesis, excitotoxicity hypothesis, and neuroinflammation hypothesis. Each hypothesis has led to the development of various drugs, but clinical trial results have questioned the significance of these hypotheses. For instance, the amyloid hypothesis has been challenged by repeated failures in Aβ-targeted clinical trials, while the tau hypothesis suggests that tau pathology may be more critical than amyloid plaques. Several challenges exist in AD treatment, including the lack of evidence for the exact mechanism and primary target, the absence of neuronal protective or regenerative drugs, and the complexity of the disease. AD is a chronic and progressive disease, requiring long-term drug safety and specific studies for each stage. Despite these challenges, there have been advances in anti-Alzheimer drugs and their mechanisms of action. Cholinergic drugs, glutamatergic drugs, phosphodiesterase inhibitors, anti-Aβ drugs, tau protein targeting drugs, and β-secretase acting drugs have shown potential in clinical trials. However, many drugs have failed due to toxicity, cognitive worsening, and lack of efficacy. The development of new drugs that target specific therapeutic targets while avoiding adverse effects remains a critical area of research.