This review provides background and perspective for the articles contributing to the Special Issue of MDPI Micro-organisms on Paramecium as a Modern Model Organism. The six articles cover a variety of topics, each taking advantage of an important aspect of Paramecium biology: peripheral surface proteins that are developmentally regulated, endosymbiont algae and bacteria, ion channel regulation by calmodulin, regulation of cell mating reactivity and senescence, and the introns that dwell in the large genome. Each article highlights a significant aspect of Paramecium and its versatility.