Pharmacists are caring for more individuals of diverse age, gender, race, ethnicity, socioeconomic status, religion, sexual orientation, and health beliefs than in previous decades. Not all residents of the United States equally experience long life spans and good health. Health disparities in various cultures have been documented. One critical aspect of reducing health disparities is moving health care providers, staff, administrators, and practices toward increased cultural competence and proficiency. Effective delivery of culturally and linguistically appropriate service in cross-cultural settings is identified as cultural competence. Culture is a dynamic process, with people moving in and out of various cultures throughout their lives. The failure to understand and respect individuals and their cultures could impede pharmaceutical care. Incongruent beliefs and expectations between the patient and pharmacist could lead to misunderstandings, confusion, and ultimately to drug misadventures. Models and frameworks have been developed that provide descriptions of the process by which individuals, practice settings, and organizations can become culturally competent and proficient. This article, the first in a five-part series, presents an overview of issues related to cultural competence in health care with an emphasis on the pharmacy profession. Also provided are definitions for cultural competence and related terms, a brief overview of health disparities and challenges to the common morality, and a discussion of models and frameworks that describe pathways to cultural competence and proficiency.