Since its inception in 2002, the PhET Interactive Simulations project at the University of Colorado Boulder has developed over 125 interactive simulations to advance science education. In addition to the goal of promoting student conceptual understanding of science, PhET simulations aim to engage students in scientific exploration and to increase student interest in science. PhET simulations are thus designed to be fun and interactive, to connect to the real world, to provide multiple representations, and to allow rapid inquiry cycles. The PhET project is guided by cognitive research on how people learn, discipline-based research on student conceptual understanding, and research on the design of educational tools. We also test each simulation using student interviews and study the use of simulations in a variety of educational settings. Based on this experience, we have developed a set of principles for creating simulations that encourage investigation and sense making. In Part I of this chapter, we introduce our theoretical perspective, project goals, and describe our design principles and process – focusing on their application to interactive chemistry simulations. In Part II, we highlight a number of simulation design challenges specific to chemistry, drawing insights from student interview results.