In the last decades, genetic research on obesity has evolved from early twin studies to contemporary gene identification efforts, revealing significant genetic influences on body weight. New genotyping and latest generation sequencing technologies have been vital in discovering these genetic factors, and aid in identifying those most at risk of obesity. Moreover, these technologiss have helped to better understand the underlying pathophysiology of obesity, which may eventually form a basis for the development of new therapies. Understanding how different genetic factors shape obesity risk, and how they can be studied by diagnostic tools, requires knowledge of the structure of the genome. In this chapter, we provide an overview of the fundamental workings of the human genome, and discuss several diagnostic tools that are used within clinical genetics to identify genetic and epigenetic causes of obesity.