Forensic science concerns the application of scientific techniques to questions of a legal nature and may also be used to address questions of historical importance. Forensic techniques are often used in legal cases that involve crimes against persons or property, and they increasingly may involve cases of bioterrorism, crimes against nature, medical negligence, or tracing the origin of food- and crop-borne disease. Given the rapid advance of genome sequencing and comparative genomics techniques, we ask how these might be used to address cases of a forensic nature, focusing on the use of microbial genome sequence analysis. Such analyses rely on the increasingly large numbers of microbial genomes present in public databases, the ability of individual investigators to rapidly sequence whole microbial genomes, and an increasing depth of understanding of their evolution and function. Suggestions are made as to how comparative microbial genomics might be applied forensically and may represent possibilities for the future development of forensic techniques. A particular emphasis is on the nascent field of genomic epidemiology, which utilizes rapid whole-genome sequencing to identify the source and spread of infectious outbreaks. Also discussed is the application of comparative microbial genomics to the study of historical epidemics and deaths and how the approaches developed may also be applicable to more recent and actionable cases.