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. 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 Guatemala 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.