Microsatellites are direct tandem DNA repeats found in all genomes. A particular class of microsatellites, called trinucleotide repeats, is responsible for a number of neurological disorders in humans. We review here our current state of knowledge on trinucleotide repeat instability, and discuss the molecular mechanisms that may be involved in trinucleotide repeat expansions leading to fatal diseases in humans. We also present original data on microsatellite distribution in several microbial genomes, and on the use of microsatellites as physical markers to accurately and easily genotype yeast strains.