The purpose of this integrative review was to examine the literature on culturally relevant healthcare interventions, and their effect on health outcomes, in an attempt to determine whether culture matters in the context of healthcare delivery. Research literature on culturally relevant interventions from the past 20 years was reviewed using computerized searches of Medline and CINAHL databases. Results of the review indicate that culturally relevant interventions significantly improve health outcomes for patients with diabetes mellitus (DM), drug addiction, sexually transmitted infections (STIs), and other health problems. It appears that the design of culturally relevant interventions does not require specific knowledge of particular ethnic or cultural groups, but of cross-cultural process principles. Because the studies are highly variable with respect to design and method, it is difficult to isolate which particular aspects of the interventions are specifically associated with favorable outcomes. In addition, few of the studies examined long-term effects of the interventions on outcomes.