We review the studies on the links between obesity, the immune system and lifestyle (limited or excessive calorie intake) that provoke changes in the current therapeutic course. There is no doubt that the positive energy balance of the body affects the immune cells, and consequently, the changes intracellular pathways, leading to the disruption of their function. Research suggests that metformin, a drug long used to treat diabetes, and an alternative remedy in the treatment of obesity, increases the activity of 5-adenosinemonophosphate (AMP)-activated kinase (AMPK). Thus, this review comes to the conclusion that alongside traditional methods, such as reducing calorie intake and increasing the energy expenditure of the body, the therapeutic outcome may be improved by implementing drugs affecting the activity of AMPK. In future, other new therapeutic options may be available. The targeting receptors or immunocompetent cells residing in adipose tissue may help to reduce the effects of obesity.