Most genetic research in the area of human obesity asks the question 'Why are certain people obese?' Considerably less attention has been paid to the question of why certain people are not obese, particularly given the obesogenic environment that permeates the western culture. We present data from human and animal studies and evolutionary arguments supporting the notion that genetic studies of thinness or obesity resistance may yield important and complementary findings to genetic studies of obesity. We offer strategies for further refining the definition of thinness, weigh the advantages and disadvantages of potential sampling strategies and suggest candidate genes for thinness or obesity resistance.