Isometric thermogenesis as applied to human energy expenditure refers to heat production resulting from increased muscle tension. While most physical activities consist of both dynamic and static (isometric) muscle actions, the isometric component is very often essential for the optimal performance of dynamic work given its role in coordinating posture during standing, walking and most physical activities of everyday life. Over the past 75 years, there has been sporadic interest into the relevance of isometric work to thermoregulatory thermogenesis and to adaptive thermogenesis pertaining to body-weight regulation. This has been in relation to (i) a role for skeletal muscle minor tremor or microvibration – nowadays referred to as ‘resting muscle mechanical activity’ – in maintaining body temperature in response to mild cooling; (ii) a role for slowed skeletal muscle isometric contraction–relaxation cycle as a mechanism for energy conservation in response to caloric restriction and weight loss and (iii) a role for spontaneous physical activity (which is contributed importantly by isometric work for posture maintenance and fidgeting behaviours) in adaptive thermogenesis pertaining to weight regulation. This paper reviews the evidence underlying these proposed roles for isometric work in adaptive thermogenesis and highlights the contention that variability in this neglected component of energy expenditure could contribute to human predisposition to obesity.