Online educators are being faced with increasingly heterogeneous student populations. Researchers and practitioners are concerned that learners studying in a culture other than their own may be at an unnecessary disadvantage for a variety of reasons including but not limited to: difficulties in studying in a second or foreign language, different communication styles, coming from a another tradition of academic discourse, and differing expectations of student and teacher roles. However, the literature to date has been mostly descriptive and anecdotal. Of note, there is a lack of larger sample-size studies with sufficient power and control of extraneous variables, to identify the effects of cultural dimensions. This study investigates: the characteristics of the particular challenges that global learners encounter in an online setting; the ways that cultural and linguistic differences manifest themselves as difficulties and opportunities in global online learning environments and the usefulness of current theories regarding the influence of culturally related factors in online learning. A large scale cross-sectional survey was conducted with participants from a large multinational non-governmental agency. This study will help close the gap in the research literature. Specifically it attempts to confirm, clarify and extend our current understanding of the differential appeal of three e-learning designs (e-training, problem-based learning, and virtual classroom) to adult professional in-service learners related to their diverse national and disciplinary cultural backgrounds. This study also includes other variables that might be more significant than, or might mediate the effects of cultural effects. Furthermore, the survey sheds some light on which theoretical cultural characteristics/dimensions seem to account for such observed differential perceptions of the three modes of e-learning.