Specialized languages used for describing computational models in the field of systems biology and physiology, such as Systems Biology Markup Language (SBML), CellML, and Physiological Hierarchy Markup Language (PHML), have been devised to enhance effective model reuse and sharing among researchers for developing large, multilevel models. Each language has its own specialty. By combining two of these languages, i. e. SBML for illustrating subcellular phenomena and PHML for expressing supracellular dynamics, a novel technology has been developed to describe models of multilevel biophysiological systems. For practical use of the aforementioned languages, consolidated software applications providing intuitive graphical user interfaces are necessary. Starting from 2011, a versatile platform called PhysioDesigner has been developed for multilevel modeling of physiological systems based on PHML. In this article, we focus on the newly developed distinguishing features of PhysioDesigner and PHML for the development of multilevel biophysiological models using SBML-PHML hybridization.