Instructional systems are products of the cultures in which they are developed. Culture, which we define here as “the collective programming of the mind which distinguishes the members of one group or category of people from another" (Hofstede, 2001), has a pervasive influence on instructional systems, regardless of whether these systems involve self-paced e-learning, synchronous or asynchronous computer-based learning activities, or online communities of learners. The issue of culture’s impact on instructional systems becomes most relevant and challenging where such systems are transferred across cultural boundaries, or developed for multiple cultures. This is currently happening in many large, globally dispersed organizations that use e-learning technologies to support the learning of their staff around the world. Theories of learning and of cultural dimensions suggest that the effectiveness of certain types of learning systems will be affected where they are used in culturally diverse environments. The aim of this paper is to highlight the issues that designers of a wide range of e-learning experiences face when designing e-learning for culturally diverse learner groups. We provide some models to support learning practitioners, focusing in particular on the importance of a conscious, culturally-informed selection of instructional strategies as the most critical part of the design and development process.