Latinos account for 15% of the US population, a proportion projected to grow to 30% by the year 2050. Although there is tremendous diversity within this community, commonalities of language, beliefs, attitudes, and behaviors unite Latinos, making them more similar than different. Differences by national origin, although important, are attenuated when immigrants come to the United States, dominated by an English-language, Anglo-centric culture. For non-Latino and non-Spanish-speaking clinicians, communication barriers and cultural misunderstandings can impede the care of dying Latino patients and their families. We present the case of a young, pregnant, Spanish-speaking woman from Central America diagnosed with a fatal leukemia. As illustrated by this case, Latino immigrants face a number of external challenges to optimal end-of-life care: (1) geographic distance as well as political and economic realities often separate patients from their valued families; (2) undocumented immigrants are frequently uninsured and fear of deportation may create a barrier to accessing health services; (3) language and literacy barriers; and (4) concerns about discrimination. Other Latino issues that may be more pronounced in end-of-life settings include cultural themes and religious and spiritual influences. We recommend that professional interpreters must be used for discussions about goals of care with Spanish-speaking patients and families or when negotiating conflict between the patient, family, and the health care team. Concrete suggestions are provided for clinicians in working with interpreters, eliciting culturally based attitudes and beliefs, and implementing universal strategies for clear health communication.