Whole genome sequences are present-day bonanzas for taxonomists. Comparative genomics provides a promising perspective to reveal the evolutionary relationship between organisms, but this strategy is not applicable for extrachromosomal elements due to their high recombination frequencies. Classification of plasmids is based on their compatibility, i.e., the ability to coexist within the same cell. Compatibility testing is a laborious experimental discipline of pairwise comparisons developed for a small set of replicons. Thus, novel approaches are urgently required to deal with the exponentially increasing amount of sequence data. In this minireview, a short overview about the functional role and distribution of plasmids as well as a summary of recent strategies to classify the replicons via phylogenetic analyses is given. Our own work essentially bases on genes of the replication module, i.e., the replicase and two conserved partitioning genes and we exemplified this approach for the four different plasmid types from Alphaproteobacteria. It is suitable for a reliable classification of these replicons and allows in silico predictions about their compatibility. The development of a general classification scheme for plasmids from all microbial lineages will ensure a systematic assessment of the upcoming data flood and help to understand the distribution of extrachromosomal elements.