The field of Synthetic Biology seeks to apply engineering principles to biology in order to produce novel biological systems. One approach to accomplish this goal is the genome-driven cell engineering approach, which searches for functioning minimal genomes in naturally occurring microorganisms, which can then be used as a template for future systems. Currently a prototypical minimal genome has not been discovered. This review analyzes the organisms Mycoplasma pneumoniae, Pelagibacter ubique, Vesicomyosocius okutanii and Prochlorococcus marinus as models of heterotrophic symbiont, heterotrophic free-living, autotrophic symbiont and autotrophic free-living organisms respectively and compares them to the current minimal cell model in order to determine which most closely resembles a true minimal genome. M. pneumoniae possesses a genome of 816 394 base pairs (bp) with 688 open reading frames (ORF) and a severely limited metabolism. Pelagibacter ubique possesses a 1 308 000 bp genome with 1354 ORF and has a fully functional metabolism but requires a reduced form of sulphur. Vesicomyosocius okutanii possesses a 1 020 000 bp genome with 975 ORF and is deficient in the production of threonine, isoleucine and ubiquinone. Prochlorococcus marinus possesses a 1 751 080 bp genome with 1884 ORF and has a complete metabolism with no deficiencies. The current minimal cell model requires a genome to be of limited size, culturalble and having minimal media requirements as such it is the conclusion of this review that P. marinus best fits this model. Further, future research should concentrate on genome reduction experiments using P. marinus and the search for additional minimal genomes should concentrate on autotrophic free-living organisms.