Direct mass spectrometry-based metabolomics has been widely employed in the last years to characterize metabolic alterations underlying to Alzheimer’s disease development and progression. This high-throughput approach presents a great potential for fast and simultaneous fingerprinting of a vast number of metabolites, which can be applied to multiple biological samples such as serum/plasma, urine, cerebrospinal fluid and tissues. In this review article we present the main advantages and drawbacks of metabolomics based on direct mass spectrometry compared with conventional analytical techniques, and provide a comprehensive revision of the literature on the application of these tools in Alzheimer’s disease research.