Flavobacterium columnare is the cause of columnaris disease, a serious condition affecting numerous freshwater fish species all over the world. Hitherto, only very scarce information is available on the pathogenesis of this bacterial disease, making it difficult to adopt a preventive approach to combat this pathogen. This study ambiates to shed more light on the way F. columnare interacts with its host. Since a number of difficulties occur in trying to isolate F. columnare from diseased fish, first of all, a selective medium was developed which enabled to recover various isolates from diseased live-bearing aquarium fish. In experimental infection studies in which these isolates were adopted, differences in virulence were noted. In a further stage, a clear correlation was made between virulence and the ability to adhere to the gill tissue, documenting the importance of the gills in the pathogenesis of columnaris disease. In this respect, a gill perfusion model was developed, by which means the adhesion of F. columnare to the gill tissue was partly pinpointed and various environmental factors influencing the adherence process elucidated. It may hence be stated that an important milestone has been achieved in the realisation of one of the most frequently used ways to prevent disease, that is through vaccination. Columnaris disease may also be opposed by ensuring good management practices eliciting adequate environmental circumstances.