Childhood obesity is a major public health challenge and its prevalence continues to increase in many, but not all, countries worldwide. International data indicate that the prevalence of obesity is greater among boys than girls 5–19 years of age in the majority of high and upper middle-income countries worldwide. Despite this observed sex difference, relatively few studies have investigated sex-based and gender-based differences in childhood obesity. We propose several hypotheses that may shape the research agenda on childhood obesity. Differences in obesity prevalence may be driven by gender-related influences, such as societal ideals about body weight and parental feeding practices, as well as sex-related influences, such as body composition and hormones. There is an urgent need to understand the observed sex differences in the prevalence of childhood obesity; incorporation of sex-based and gender-based analysis in all childhood obesity studies may ultimately contribute to improved prevention and treatment.