Numerous studies have shown that feeding rodents n-3 polyunsaturated fatty acids attenuates adiposity. Moreover, meta-analyses of human dietary intervention studies indicate that fish oil (eicosapentaenoic and docosahexaenoic acid) supplementation might reduce waist circumference. A recent line of research suggests that browning of white adipose depots and activation of uncoupled respiration in brown fat contributes to these effects. This mini-review summarizes the observations in rodents, highlights several mechanisms that might explain these observations and discusses the translational potential. Given the available in vivo evidence and the ability of human adipocytes to aquire a beige phenotype in response to eicosapentaenoic acid incubation, future studies should test the hypothesis that fish oil activates thermogenic brown and beige adipose tissue in humans.