Objectives: Alzheimer's disease (AD) is a neurodegenerative disease primarily of the elderly, and treatment modalities are limited. AD is characterized by the presence of senile plaques with its main component amyloid â , neurofibrillary tangles with phosphophorylated tau protein, and neuronal loss. These pathological components as well as inflammation are hypothesized to be involved in the pathogenesis of AD. When considering potential treatment modalities for AD, this pathogenesis should be considered. Periostat is a drug containing low dosages of Doxycycline and is used in long-term administration to treat periodontal disease without the side effects characterizing the anti-microbial doses of this medication. The objective of this study is to evaluate the possible use of Periostat for treating AD by critically analyzing the existing literature. Methods: a Medline search was undertaken using combinations of the following terms: doxycycline, tetracycline, minocycline, Alzheimer's disease, cognition, mild impairment cognition, metalloproteinase (MMP), amyloid, and inflammation. Then, the relevant papers were reviewed manually. Results: the database search resulted in a total 301 papers containing the search terms. Further evaluation resulted in 45 papers containing relevant data. The studies evaluated were based on in vitro, animal, and clinical data. Only one randomized control study was found. The review study found that tetracycline derivatives, including doxycycline: a) cross the brain blood barrier; b) have neuroprotective effects; c) destabilize the amyloid fibrils to make them susceptible to proteolysis; d) inhibit caspase-3 that has a role in tau protein neurotoxicity; e) inhibit the production of proinflammatory molecules; and f) slow cognitive decline. However, untoward effects have also been reported related to tetracyclines anti-MMPs activities. Conclusion: the available data suggest that in selective cases low dosage doxycycline may be effective in treating AD.