The motor-evoked potential (MEP) elicited in peripheral muscles by transcranial magnetic stimulation (TMS) over human motor cortex is one of the hallmark measures for non-invasive quantification of cortical and spinal excitability in cognitive and clinical neuroscience. In the present article, we distinguish three main uses for MEPs in studies of behaviour: for understanding execution and performance of actions, as markers of physiological change in the motor system, and as read-out of upstream processes influencing the motor system. Common to all three approaches is the assumption that different experimental manipulations act on the balance of excitatory and inhibitory pre-synaptic (inter)neurons at the stimulation site; this in turn contributes to levels of (post-synaptic) excitability of cortico-spinal output projections, which ultimately determines the size of MEPs recorded from peripheral muscles. We discuss the types of inference one can draw from human MEP measures given that the detailed physiological underpinnings of MEPs elicited by TMS are complex and remain incompletely understood. Awareness of the different mechanistic assumptions underlying different uses of MEPs can help inform both study design and interpretation of results obtained from human MEP studies of behaviour.