Dr. Bustamante's laboratory works on a variety of organisms and model systems ranging from humans and other primates to domesticated plant and animals. Much of their research is at the interface of computational biology, mathematical genetics, and evolutionary genomics. Examples of their research accomplishments include:

• Developing selection maps of the human genome which pinpoint rapidly evolving genes as well as genomic regions subject to strong selective constraint;
• Developing a high-density map of genetic variation in the dog genome and using it to identify genomic regions underlying morphological differences among domestic dog breeds;
• Investigating the fine scale genetic structure of human populations and its implication for genomic medicine.

Their  current research focuses on human population genomics and global health including developing statistical, computational, and genomic resources for enabling trans- and multi-ethnic genome-wide association and medical sequencing studies of complex biomedical traits.