This article presents recent findings from several long-term qualitative investigations of co-teaching in science and social studies content-area classes, in which collaborating teachers and students with and without disabilities were observed and interviewed regarding effective practices and challenges associated with inclusion. In some sites, collaborating teachers were provided with research-based effective strategies and materials for including students with disabilities in specific activities. Results were equivocal in that in some cases, collaboration was extremely effective and conducive for promoting success for students with disabilities in inclusive classes. In others, challenges remained that presented barriers for successful collaboration and inclusion for students with disabilities. Important mediating variables were identified as academic content knowledge, high-stakes testing, and co-teacher compatibility. Findings are discussed with respect to both successes and remaining challenges.