Numerous national initiatives call for interdisciplinary mathematics and science education, but few empirical studies have examined practical considerations for integrated instruction in high school settings. The purpose of this qualitative study was twofold. First, the study sought to describe how and to what extent teachers integrate mathematics and science curricula in their classrooms after having participated in an intervention to promote and support mathematics and science integration. Second, the study was intended to expand our understanding of the barriers to and factors that enable integrated approaches in high school classrooms. The theoretical component of this study builds on and adapts previous models of science and mathematics integration to introduce the Intradisciplinary, Cross-disciplinary, Multidisciplinary, Interdisciplinary (ICMI) framework for identifying and defining classroom integration strategies. Findings include a description of several distinct practices high school teachers related to integrated instruction as well as the trade-offs teachers considered when making decisions related to integrated curricula. The implications of the findings for researchers and practitioners are discussed. Finally, we propose the conceptualization of "interdisciplinary pedagogical content knowledge" in mathematics and science as an area of focus that will enable teachers to successfully move toward interdisciplinary instruction.