Brown and beige adipose tissues play a large role in non-shivering thermogenesis (NST) in mammals, and subsequently have been studied for decades as potential therapeutic targets to treat obesity and its related metabolic diseases. However, the mechanistic regulation of brown/beige adipose tissue induction and maintenance in humans is very limited due to the ethical reasons. In fact, metabolic signaling has primarily been investigated using rodent models. A better understanding of non-shivering thermogenesis in humans is thus vital and urgent in order to treat obesity by targeting human brown adipose tissue (BAT). In this review, we summarize the anatomical and physiological differences between rodent and human BAT, current useful and mostly non-invasive methods in studying human BAT, as well as recent advancements targeting thermogenic adipocytes as a means to combat metabolic diseases in humans. Furthermore, we also discuss several novel relevant strategies of therapeutic interventions, which has been attempted in rodent experiments, and possible future investigations in humans in this field.