“...we must make an attempt to species definition. In doing so we are confronted by the paradoxical incongruity of trying to establish a fixed stage in the evolutionary stream. If there is evolution in the true sense of the word, as against catastrophism or creation, we should find all kind of species – incipient species, mature species, incipient genera, as well as all intermediate conditions” (Ernst Mayer, 1942, Systematics and the origin of species). This is the sentence opening R.F. Withcomb presentation for his EKN award in 1994, just twenty years ago, when I attended my first IOM meeting. Since then the study of phytopathogenic mycoplasmas (or phytoplasmas) was mainly devoted toward their classification based on molecular dissecting of their ribosomal DNA and of other conserved genes. The availability of a robust and quite exhaustive classification system allowed recently to also developing barcodes capable to identify them. However this research could end in a sterile play, producing shopping lists of genotypes, if the knowledge of phytoplasma biology is not accompanying their taxonomy. We gained a lot of information from full genome sequencing on putative biochemical pathways, all showing that phytoplasmas are very special microorganisms because they lack a lot for relevant features: cell wall, mobility, key enzymes and pathways. What they have is a small efficient chromosome and tricky metabolisms, allowing them to a trans kingdom life of interaction that often increase activity of their hosts enhancing insect fitness, plant shoot production, changing shape and colour of flowers. For some of them it looks also that they are preparing to become relevant permanent cell hosts. However they are still far from loosing independence and freedom as they can also act as very dangerous pathogens for many relevant agricultural crops. Biology represents still the much unknown part of phytopathogenic mycoplasmas; but recently as a small step toward opening the study of their biology was achieved, and the confirmation of the huge amount of molecular information gained in the last twenty years of research is waiting. Only the knowledge of their day by day biology will help in defining feasible solutions to reduce phytoplasma impact on worldwide agriculture suggesting the best management strategy. Just we need to remember that to win the enemy we must know him very well.