An eccentric contraction involves the active lengthening of muscle under an external load. The molecular and neural mechanisms underpinning eccentric contractions differ from those of concentric and isometric contractions and remain less understood. A number of molecular theories have been put forth to explain the unexplained observations during eccentric contractions that deviate from the predictions of the established theories of muscle contraction. Postulated mechanisms include a strain-induced modulation of actin-myosin interactions at the level of the cross-bridge, the activation of the structural protein titin, and the winding of titin on actin. Accordingly, neural strategies controlling eccentric contractions also differ with a greater, and possibly distinct, cortical activation observed despite an apparently lower activation at the level of the motor unit. The characteristics of eccentric contractions are associated with several acute physiological responses to eccentrically-emphasised exercise. Differences in neuromuscular, metabolic, hormonal and anabolic signalling responses during, and following, an eccentric exercise bout have frequently been observed in comparison to concentric exercise. Subsequently, the high levels of muscular strain with such exercise can induce muscle damage which is rarely observed with other contraction types. The net result of these eccentric contraction characteristics and responses appears to be a novel adaptive signal within the neuromuscular system.