An incremental ramp exercise is a protocol that is frequently used in the domain of exercise testing to get an insight into the exercise tolerance of both healthy active populations (including athletes) and patients, due to the specific characteristics of the protocol. The continuous and linear increase in work rate is not only less strenuous for populations with a very low exercise capacity but it requires the aerobic metabolism to adapt to the continuously changing conditions. Therefore, this protocol can provide important information on the adaptive capacity of individuals to exercise in non-steady-state conditions. The ramp exercise has also been used in the past two decades to get an insight into the underlying mechanisms of the oxygen uptake (·VO₂) response (and kinetics) to exercise. Against the expectations, it has been shown that the parameters that quantify the ·VO₂ response to ramp exercise do not completely correspond to those obtained from constant work-rate transitions and incremental step exercise. For that reason, it could be concluded that the ·VO₂ response is specific to ramp exercise, and thus is determined by other mechanisms than those which determine other protocols. Although the ·VO₂ response to ramp exercise has a high level of reproducibility and a uniform pattern can be observed, especially for the ·VO₂ response below the gas exchange threshold (GET) [above the GET, the ·VO₂ response is less clear], some prudence is necessary when interpreting potential differences in the ·VO₂ response between populations. Several methodological issues (e.g. baseline work rate, ramp slope) exert an important impact on the ·VO₂ response to ramp exercise. The main purpose of this review is to provide an overview of the methodological and physiological factors that have an impact on the ·VO₂ response to ramp exercise. It is of importance that exercise physiologists take these factors into consideration, not only prior to the conductance of the ramp exercise in a variety of subjects, but also when interpreting the obtained results.