The adipose organ portrays adipocytes of diverse tones: white, brown and beige, each type with distinct functions. Adipocytes orchestrate their adaptation and expansion to provide storage to excess nutrients, the quick mobilisation of fuel to supply peripheral functional demands, insulation, and, in their thermogenic form, heat generation to maintain core body temperature. Thermogenic adipocytes could be targets for anti-obesity and anti-diabetic therapeutic approaches aiming to restore adipose tissue functionality and increase energy dissipation. However, for thermogenic adipose tissue to become therapeutically relevant, a better understanding of its development and origins, its progenitors and their characteristics and the composition of its niche, is essential. Also crucial is the identification of stimuli and molecules promoting its specific differentiation and activation. Here we highlight the structural/cellular differences between human and rodent brown adipose tissue and discuss how obesity and metabolic complication affects brown and beige cells as well as how they could be targeted to improve their activation and improve global metabolic homeostasis. Finally, we describe the limitations of current research models and the advantages of new emerging approaches.