Introduction: The human microbiome is a compendium of all organisms on and within the human body (i.e., bacteria, archaea, fungi, and eukaryotes), where the diversity of taxa as well as their relative abundance contribute to the highly individualizing nature of an individual's microbial signature. Discussion: The effect of individual characteristics such as lifestyle, genetics, health, and geographic provenance on the human microbiome contribute to both the individuality and forensic usefulness of microbiome samples for the purposes of human identification, body fluid attribution, estimation of the post-mortem interval, or geolocation. Further, the use of technologies such as massively parallel sequencing and long-read sequencing, in combination with bioinformatic tools and machine learning models, allow for quick and accurate characterization of individual human microbiome samples. Conclusion: However, before microbial profiling can be implemented into routine forensic casework, extensive standardization and validation of sample types, collection procedures and analysis pipelines must be established.