In August 2006 the Center for Human Genomics of the Wake Forest University School of Medicine in Winston-Salem, NC hosted the NIH-sponsored Roadmap Course entitled Models and Technologies for Defining Phenotype. Twenty-four biomedical and genomic researchers from throughout the world and with varying degrees of experience in the Genomics, Biological, and Biomedical Engineering Sciences were invited to participate as students in a comprehensive course dedicated to presenting and evaluating current and future approaches that can overcome the problems experienced to date in characterizing the functional consequences of gene variation. A total of 34 senior researchers from four different academic institutions served as course faculty and employed a pedagogical approach that emphasized hands-on workshops, demonstrations, and small group discussions and tasks. Through this report we convey the complex and formidable problems unique to Genomics research as we attempt to link the field of genomic research to complex human diseases. Furthermore, we describe the logic and organization of a Roadmap Course designed to teach a diverse group of researchers a multi-disciplinary approach to addressing complex biomedical scenarios in the field of human Genomics.